Lgr5

Summary

Gene Symbol: Lgr5
Description: leucine rich repeat containing G protein coupled receptor 5
Alias: FEX, Gpr49, leucine-rich repeat-containing G-protein coupled receptor 5, G protein-coupled receptor 49, follicle expressed hormone, orphan G-protein coupled receptor FEX
Species: mouse

Top Publications

  1. doi Transcription factor achaete scute-like 2 controls intestinal stem cell fate
    Laurens G van der Flier
    Hubrecht Institute KNAW and University Medical Center Utrecht, Uppsalaan, The Netherlands
    Cell 136:903-12. 2009
  2. doi Distinct stem cells contribute to mammary gland development and maintenance
    Alexandra Van Keymeulen
    Universite Libre de Bruxelles, IRIBHM, Brussels B 1070, Belgium
    Nature 479:189-93. 2011
  3. doi Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine
    Kenichiro Furuyama
    Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
    Nat Genet 43:34-41. 2011
  4. pmc Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells
    Robert K Montgomery
    Division of Gastroenterology, Children s Hospital Boston, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:179-84. 2011
  5. pmc Wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes
    Maria Kasper
    Center for Biosciences and Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden
    Proc Natl Acad Sci U S A 108:4099-104. 2011
  6. doi Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas
    Sarah Kozar
    Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
    Cell Stem Cell 13:626-33. 2013
  7. pmc In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
    Meritxell Huch
    Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Centre Utrecht, Netherlands
    Nature 494:247-50. 2013
  8. pmc Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors
    Fuxin Shi
    Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 110:13851-6. 2013
  9. pmc Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo
    Roxana C Mustata
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Faculty of Medicine, Universite Libre de Bruxelles, Route de Lennik 808, Brussels 1070, Belgium
    EMBO Rep 12:558-64. 2011
  10. pmc Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations
    Marina Grachtchouk
    Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    J Clin Invest 121:1768-81. 2011

Scientific Experts

  • Sudhansu K Dey
  • Weilun Sun
  • Roland Rad
  • William E Lowry
  • Fuxin Shi
  • Karin E de Visser
  • Nick Barker
  • Michael Quante
  • Yoshitatsu Sei
  • Andrew G Polson
  • Serge Nef
  • Andrea Haegebarth
  • Hans Clevers
  • Johan H van Es
  • Marc van de Wetering
  • Daniel E Stange
  • Hugo J Snippert
  • Toshiro Sato
  • Maaike van den Born
  • Kelli L VanDussen
  • Ying Feng
  • Norifumi Takeda
  • Bon Kyoung Koo
  • Renjie Chai
  • Tae Hee Kim
  • Robert G Vries
  • Maria Kasper
  • Viljar Jaks
  • Sarah Schwitalla
  • Frederic J De Sauvage
  • Makoto M Taketo
  • Douglas J Winton
  • Owen J Sansom
  • Mahalia E Page
  • Linda C Samuelson
  • Kelley S Yan
  • Arnout G Schepers
  • Alexander van Oudenaarden
  • Shabaz Mohammed
  • Albert J R Heck
  • Shalev Itzkovitz
  • Peter J Peters
  • Pekka Kujala
  • Marie Isabelle Garcia
  • Xiaofei Sun
  • Rune Toftgard
  • Laurens G van der Flier
  • Vera Shirokova
  • Victoria Llado
  • Amelie Boquoi
  • Elise S Demitrack
  • Eric R Fearon
  • Kathleen R Cho
  • Karyn L Sheaffer
  • Laila Ritsma
  • Ciara Metcalfe
  • Alexandra Wiese
  • Zoltan Wiener
  • Ryotaro Sakamori
  • Wenwen Ren
  • Theresa M Keeley
  • Alexis J Carulli
  • Louis Vermeulen
  • Bohumil Fafilek
  • S Radulescu
  • Toshihiro Tanaka
  • Akihiro Hirata
  • Sarah Kozar
  • Eric Vroegindeweij
  • Simon J A Buczacki
  • Wei Jie Zhou
  • Richard Kemp
  • Meritxell Huch
  • Evan R Barry
  • David J Huels
  • Patrizia Cammareri
  • Yunhua Zhu
  • Anna M Nicholson
  • Andrea Flesken-Nikitin
  • C Gil-Sanchis
  • Florian R Greten
  • Kevin B Myant
  • Scott T Magness
  • Kim B Jensen
  • Sylvie Robine
  • Calvin J Kuo
  • Nobuo Sasaki
  • Jonathan A Epstein
  • Jacco van Rheenen
  • M Leushacke

Detail Information

Publications96

  1. doi Transcription factor achaete scute-like 2 controls intestinal stem cell fate
    Laurens G van der Flier
    Hubrecht Institute KNAW and University Medical Center Utrecht, Uppsalaan, The Netherlands
    Cell 136:903-12. 2009
    ..We recently demonstrated the existence of a long-lived pool of cycling stem cells defined by Lgr5 expression and intermingled with post-mitotic Paneth cells at crypt bottoms...
  2. doi Distinct stem cells contribute to mammary gland development and maintenance
    Alexandra Van Keymeulen
    Universite Libre de Bruxelles, IRIBHM, Brussels B 1070, Belgium
    Nature 479:189-93. 2011
    ....
  3. doi Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine
    Kenichiro Furuyama
    Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
    Nat Genet 43:34-41. 2011
    ..These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status...
  4. pmc Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells
    Robert K Montgomery
    Division of Gastroenterology, Children s Hospital Boston, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:179-84. 2011
    The intestinal epithelium is maintained by a population of rapidly cycling (Lgr5(+)) intestinal stem cells (ISCs)...
  5. pmc Wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes
    Maria Kasper
    Center for Biosciences and Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden
    Proc Natl Acad Sci U S A 108:4099-104. 2011
    ....
  6. doi Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas
    Sarah Kozar
    Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
    Cell Stem Cell 13:626-33. 2013
    ..These findings suggest that the bulk of tumor stem cell divisions serve only to replace stem cell loss, with rare clonal victors driving gland repopulation and tumor growth...
  7. pmc In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
    Meritxell Huch
    Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Centre Utrecht, Netherlands
    Nature 494:247-50. 2013
    The Wnt target gene Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles...
  8. pmc Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors
    Fuxin Shi
    Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 110:13851-6. 2013
    ..We recently identified leucine-rich repeat containing, G-protein-coupled receptor 5 (Lgr5)-expressing cochlear supporting cells with the capacity for self-renewal and hair cell differentiation in vitro...
  9. pmc Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo
    Roxana C Mustata
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Faculty of Medicine, Universite Libre de Bruxelles, Route de Lennik 808, Brussels 1070, Belgium
    EMBO Rep 12:558-64. 2011
    Gene inactivation of the orphan G protein-coupled receptor LGR4, a paralogue of the epithelial-stem-cell marker LGR5, results in a 50% decrease in epithelial cell proliferation and an 80% reduction in terminal differentiation of Paneth ..
  10. pmc Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations
    Marina Grachtchouk
    Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    J Clin Invest 121:1768-81. 2011
    ....
  11. doi Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling
    Wim de Lau
    Hubrecht Institute and University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
    Nature 476:293-7. 2011
    The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments...
  12. pmc A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable
    Hua Tian
    Department of Molecular Biology, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 478:255-9. 2011
    ..One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base...
  13. pmc Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice
    Katrin Arnold
    Howard Hughes Medical Institute and Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, Cambridge, MA 02138, USA
    Cell Stem Cell 9:317-29. 2011
    ..Thus, our results identify Sox2 expression in numerous adult endodermal and ectodermal stem cell compartments, which are critical for normal tissue regeneration and survival...
  14. pmc Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
    Toshiro Sato
    Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Nature 469:415-8. 2011
    Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms...
  15. pmc Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection
    Wei Jie Zhou
    Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
    Nature 501:107-11. 2013
    ..Therefore Rspo1 and Slit2 may act as therapeutic adjuvants to enhance host tolerance to aggressive chemoradiotherapy for eradicating metastatic cancers. ..
  16. doi Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer
    M Leushacke
    A STAR Institute of Medical Biology, 8A Biomedical Grove, 06 06 Immunos, Singapore
    Oncogene 31:3009-22. 2012
    ..However, the 7-transmembrane receptor, Lgr5 has recently gained prominence as a marker of Wnt-regulated adult stem cell populations in the hair-follicle, ..
  17. pmc Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells
    Tae Hee Kim
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:3932-7. 2012
    ..b>Lgr5 and Bmi1 are two molecular markers of crypt-cell populations that replenish all lineages over time and hence ..
  18. pmc Interconversion between intestinal stem cell populations in distinct niches
    Norifumi Takeda
    Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 334:1420-4. 2011
    ..Conversely, CBCs can give rise to +4 Hopx-positive cells. These findings demonstrate a bidirectional lineage relationship between active and quiescent stem cells in their niches...
  19. doi Intestinal label-retaining cells are secretory precursors expressing Lgr5
    Simon J A Buczacki
    Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
    Nature 495:65-9. 2013
    ..These findings establish quiescent cells as an effective clonogenic reserve and provide a motivation for investigating their role in pathologies such as colorectal cancers and intestinal inflammation...
  20. pmc Single-molecule transcript counting of stem-cell markers in the mouse intestine
    Shalev Itzkovitz
    Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Cell Biol 14:106-14. 2011
    ..We find that the expression of all markers overlaps at crypt-base cells. This co-expression includes Lgr5, Bmi1 and mTert, genes previously suggested to mark distinct stem cells...
  21. pmc The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations
    Kelley S Yan
    Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 109:466-71. 2012
    ..Bmi1 and Lgr5 have been independently identified to mark long-lived multipotent ISCs by lineage tracing in mice; however, the ..
  22. pmc Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells
    Kelli L VanDussen
    Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, MI 48109, USA
    Development 139:488-97. 2012
    ..Our findings suggest that Notch targets distinct progenitor cell populations to maintain adult intestinal stem cells and to regulate cell fate choice to control epithelial cell homeostasis...
  23. doi Apoptosis differently affects lineage tracing of Lgr5 and Bmi1 intestinal stem cell populations
    Yunhua Zhu
    Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore
    Cell Stem Cell 12:298-303. 2013
    ..We found that about 40% of apoptotic cells were Lgr5-positive whereas Bmi1-positive ISCs became sensitive to tamoxifen upon entering a proliferative state...
  24. pmc Spasmolytic polypeptide-expressing metaplasia (SPEM) in the gastric oxyntic mucosa does not arise from Lgr5-expressing cells
    Ki Taek Nam
    Nashville VA Medical Center and the Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2733, USA
    Gut 61:1678-85. 2012
    ..that cells demonstrating transcriptional activity for leucine-rich repeat containing G-protein-coupled receptor 5 (Lgr5) in the intestine, colon and gastric antrum function as adult stem cells...
  25. doi Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
    Toshiro Sato
    Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Nature 459:262-5. 2009
    ..We have recently demonstrated the presence of about six cycling Lgr5(+) stem cells at the bottoms of small-intestinal crypts...
  26. pmc Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea
    Fuxin Shi
    Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 32:9639-48. 2012
    ..We show here that Lgr5, a marker for adult stem cells, was expressed in a subset of supporting cells in the newborn and adult murine ..
  27. doi Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas
    Arnout G Schepers
    Hubrecht Institute, Koninklijke Nederlandse Akademie van Wetenschappen, and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands
    Science 337:730-5. 2012
    ..lineage retracing" using the multicolor Cre-reporter R26R-Confetti, we demonstrate that the crypt stem cell marker Lgr5 (leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5) also marks a ..
  28. ncbi Identification of stem cells in small intestine and colon by marker gene Lgr5
    Nick Barker
    Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Nature 449:1003-7. 2007
    ..Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression...
  29. pmc The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers
    Javier Munoz
    Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences, University, The Netherlands
    EMBO J 31:3079-91. 2012
    ..Here, we combine transcriptomics with proteomics to define a definitive molecular signature for Lgr5(+) CBC cells...
  30. pmc G-protein-coupled receptor GPR49 is up-regulated in basal cell carcinoma and promotes cell proliferation and tumor formation
    Keiji Tanese
    Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Am J Pathol 173:835-43. 2008
    ..formation in BCC, we screened a DNA microarray database of human BCC cases; the orphan G-protein-coupled receptor GPR49 was found to be up-regulated in all cases...
  31. doi Lgr5 marks cycling, yet long-lived, hair follicle stem cells
    Viljar Jaks
    Karolinska Institutet, Department of Biosciences and Nutrition, Novum, SE 141 57 Huddinge, Sweden
    Nat Genet 40:1291-9. 2008
    In mouse hair follicles, a group of quiescent cells in the bulge is believed to have stem cell activity. Lgr5, a marker of intestinal stem cells, is expressed in actively cycling cells in the bulge and secondary germ of telogen hair ..
  32. doi Crypt stem cells as the cells-of-origin of intestinal cancer
    Nick Barker
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht and University Medical Centre Utrecht, Netherlands
    Nature 457:608-11. 2009
    ..As in most cancers, the cell of origin has remained elusive. In a previously established Lgr5 (leucine-rich-repeat containing G-protein-coupled receptor 5) knockin mouse model, a tamoxifen-inducible Cre ..
  33. pmc Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation
    Liqin Zhu
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA
    Nature 457:603-7. 2009
    ..reporter allele showed that Prom1(+) cells are located at the base of crypts in the small intestine, co-express Lgr5 (ref. 2), generate the entire intestinal epithelium, and are therefore the small intestinal stem cell...
  34. pmc Dll1+ secretory progenitor cells revert to stem cells upon crypt damage
    Johan H van Es
    Hubrecht Institute for Developmental Biology and Stem Cell Research and Univerity Medical Centre Utrecht, Utrecht, Netherlands
    Nat Cell Biol 14:1099-104. 2012
    b>Lgr5+ intestinal stem cells generate enterocytes and secretory cells. Secretory lineage commitment requires Notch silencing. The Notch ligand Dll1 is expressed by a subset of immediate stem cell daughters...
  35. pmc Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium
    Akihiro Hirata
    Division of Animal Experiment, Life Science Research Center, Gifu University, 1 1 Yanagido, Gifu, 501 1194, Japan
    Development 140:66-75. 2013
    ..We show that elevated levels of Wnt signalling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells...
  36. doi LGR5 deficiency deregulates Wnt signaling and leads to precocious Paneth cell differentiation in the fetal intestine
    Marie Isabelle Garcia
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire IRIBHM, Faculty of Medicine, Universite Libre de Bruxelles, 1070 Brussels, Belgium
    Dev Biol 331:58-67. 2009
    The orphan Leucine-rich repeat G protein-coupled receptor 5 (LGR5/GPR49), a target of Wnt signaling, is a marker of adult intestinal stem cells (SC)...
  37. doi Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties
    Sarah Schwitalla
    Institute of Molecular Immunology, Klinikum rechts der Isar, Technische Universitat Munchen, 81675 Munich, Germany
    Cell 152:25-38. 2013
    ..Thus, our data support the concept of bidirectional conversion and highlight the importance of inflammatory signaling for dedifferentiation and generation of tumor-initiating cells in vivo...
  38. pmc The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor
    Anne E Powell
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Cell 149:146-58. 2012
    ..Transcriptome profiling of Lrig1(+) colonic stem cells differs markedly from the profiling of highly proliferative, Lgr5(+) colonic stem cells; genes upregulated in the Lrig1(+) population include those involved in cell cycle repression ..
  39. pmc Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling
    Vivian W Y Wong
    The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge CB2 0SZ, UK
    Nat Cell Biol 14:401-8. 2012
    ..Our findings reveal ErbB activation as a strong inductive signal for stem-cell proliferation. This has implications for our understanding of ErbB signalling in tissue development and maintenance and the progression of malignant disease...
  40. doi Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro
    Nick Barker
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht and University Medical Centre Utrecht, Netherlands
    Cell Stem Cell 6:25-36. 2010
    ..The Wnt target gene Lgr5 marks stem cells in the small intestine, colon, and hair follicle...
  41. doi Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin
    Hugo J Snippert
    Hubrecht Institute KNAW Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands
    Science 327:1385-9. 2010
    ..We generated knock-in alleles of murine Lgr6, a close relative of the Lgr5 stem cell gene. Lgr6 was expressed in the earliest embryonic hair placodes...
  42. pmc Mouse atonal homolog 1 directs intestinal progenitors to secretory cell rather than absorptive cell fate
    Kelli L VanDussen
    Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, MI 48109, USA
    Dev Biol 346:215-23. 2010
    ..Thus, Math1 is a key effector directing multipotential precursors to adopt secretory and not absorptive cell fate...
  43. doi Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells
    Hugo J Snippert
    Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Cell 143:134-44. 2010
    Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at the small intestinal crypt base and divide every day...
  44. pmc Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging
    Laila Ritsma
    1 Cancer Genomics Netherlands, Hubrecht Institute KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands 2
    Nature 507:362-5. 2014
    ..In addition to the Lgr5 marker, intestinal stem cells have been associated with other markers that are expressed heterogeneously within the ..
  45. doi Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration
    Ciara Metcalfe
    Molecular Oncology Department, Genentech, South San Francisco, CA 94080, USA
    Cell Stem Cell 14:149-59. 2014
    The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs)...
  46. pmc The epidermis comprises autonomous compartments maintained by distinct stem cell populations
    Mahalia E Page
    Wellcome Trust Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, CB2 1QR Cambridge, UK Department of Oncology, University of Cambridge, CB2 0QQ Cambridge, UK
    Cell Stem Cell 13:471-82. 2013
    ..In summary, our data demonstrate that epidermal stem cells are lineage restricted during homeostasis and suggest that compartmentalization may constitute a conserved mechanism underlying epithelial tissue maintenance. ..
  47. doi Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) as a putative human endometrial stem cell marker
    C Gil-Sanchis
    Fundación IVI Instituto Universitario IVI Universidad de Valencia, INCLIVA, Valencia, Spain
    Mol Hum Reprod 19:407-14. 2013
    ..tracing studies indicates that a surface protein named Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a marker that can identify SSC in several tissues such as small intestine mucosa (endodermal origin), hair ..
  48. pmc Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation
    Vera Shirokova
    Research Program in Developmental Biology, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
    Stem Cells 34:1896-908. 2016
    ..Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. Stem Cells 2016;34:1896-1908. ..
  49. pmc DNA methylation is required for the control of stem cell differentiation in the small intestine
    Karyn L Sheaffer
    Department of Genetics, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 28:652-64. 2014
    ..We establish that the loss of DNA methylation at intestinal stem cell gene enhancers causes inappropriate gene expression and delayed differentiation. ..
  50. pmc Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-β
    Zoltan Wiener
    Translational Cancer Biology Program and
    Proc Natl Acad Sci U S A 111:E2229-36. 2014
    ..and human ex vivo 3D intestinal organoid cultures and in vivo mouse models to study the effect of TGF-β on the Lgr5(+) intestinal stem cells and their progeny in intestinal adenomas...
  51. pmc CDC42 inhibition suppresses progression of incipient intestinal tumors
    Ryotaro Sakamori
    Department of Biological Sciences, Rutgers University, Newark, New Jersey
    Cancer Res 74:5480-92. 2014
    ....
  52. pmc Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo
    Wenwen Ren
    Monell Chemical Senses Center, Philadelphia, PA 19104
    Proc Natl Acad Sci U S A 111:16401-6. 2014
    Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues...
  53. pmc Reversible cell cycle inhibition and premature aging features imposed by conditional expression of p16Ink4a
    Amelie Boquoi
    Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA Department of Medicine, Fox Chase Cancer Center, Philadelphia, PA, USA
    Aging Cell 14:139-47. 2015
    ..Broad induction at weaning inhibited proliferation of intestinal transit-amplifying and Lgr5+ stem cells and rapidly imposed features of aging, including hair loss, skin wrinkling, reduced body weight and ..
  54. pmc Repression of Intestinal Stem Cell Function and Tumorigenesis through Direct Phosphorylation of β-Catenin and Yap by PKCζ
    Victoria Llado
    Cell Death and Survival Networks Program, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Rep . 2015
    ..The β-catenin and Yap pathways in Lgr5+ stem cells have been shown to be central to this process...
  55. pmc Notch signaling regulates gastric antral LGR5 stem cell function
    Elise S Demitrack
    Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI, USA
    EMBO J 34:2522-36. 2015
    ..Here we report that Notch signaling is essential for homeostasis of LGR5(+) antral stem cells...
  56. pmc Tissue-Specific Effects of Reduced β-catenin Expression on Adenomatous Polyposis Coli Mutation-Instigated Tumorigenesis in Mouse Colon and Ovarian Epithelium
    Ying Feng
    Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS Genet 11:e1005638. 2015
    ..of key β-catenin/TCF-regulated target genes, including those encoding the EphB2/B3 receptors, the stem cell marker Lgr5, and Myc, leading to maintenance of crypt compartmentalization and restriction of stem and proliferating cells to ..
  57. pmc Conditional deletion of menin results in antral G cell hyperplasia and hypergastrinemia
    Natalia A Veniaminova
    Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, 48109 2200, USA
    Am J Physiol Gastrointest Liver Physiol 303:G752-64. 2012
    ..Therefore, we examined whether conditional deletion of Men1 (Villin-Cre and Lgr5-EGFP-IRES-CreERT2), with subsequent loss of menin from the gastrointestinal epithelium, increases gastrin ..
  58. pmc SACK-expanded hair follicle stem cells display asymmetric nuclear Lgr5 expression with non-random sister chromatid segregation
    Yang Hoon Huh
    Programs in Regenerative Biology and Cancer Biology, Adult Stem Cell Technology Center, Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA, USA
    Sci Rep 1:176. 2011
    ..segregation, a unique property of distributed stem cells (DSCs), like HF-SCs, and a recently described biomarker, Lgr5. We found that nuclear Lgr5 expression was limited to the HF-SC sister of asymmetric self-renewal divisions that ..
  59. pmc E-cadherin is required for intestinal morphogenesis in the mouse
    Benjamin J Bondow
    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Dev Biol 371:1-12. 2012
    ..In summary, our data demonstrate that E-cadherin is essential for intestinal epithelial morphogenesis and homeostasis during embryonic development...
  60. doi Myb controls intestinal stem cell genes and self-renewal
    Dane Cheasley
    Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Stem Cells 29:2042-50. 2011
    ..Here, we show that transcription factor Myb governs ISC gene expression, particularly Lgr5. Lgr5 is associated with cells that have the capacity to generate all cell lineages in SI organoid cultures and ..
  61. pmc Sox9 induction, ectopic Paneth cells, and mitotic spindle axis defects in mouse colon adenomatous epithelium arising from conditional biallelic Apc inactivation
    Ying Feng
    Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Am J Pathol 183:493-503. 2013
    ..mitotic spindle misorientation, β-catenin nuclear localization, and induction of the intestinal stem cell markers Lgr5 and Musashi-1 and the Sox9 transcription factor...
  62. pmc ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation
    Kevin B Myant
    Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
    Cell Stem Cell 12:761-73. 2013
    ..We find that RAC1 is required for expansion of the LGR5 intestinal stem cell (ISC) signature, progenitor hyperproliferation, and transformation...
  63. doi Identification of stem cells that maintain and regenerate lingual keratinized epithelial cells
    Toshihiro Tanaka
    Department of Stem Cell Pathology, Kansai Medical University, 2 5 1 Shin machi, Hirakata shi, Osaka 573 1010, Japan
    Nat Cell Biol 15:511-8. 2013
    ..Taken together, these results suggest that the stem cells identified in this study are important for tissue maintenance and regeneration of the lingual epithelium...
  64. pmc Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells
    Norifumi Takeda
    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Development 140:1655-64. 2013
    ..These cells co-express Lgr5, do not express Shh and escape catagen-induced apoptosis...
  65. pmc Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche
    Andrea Flesken-Nikitin
    Department of Biomedical Sciences and Cornell Stem Cell Program, Cornell University, Ithaca, New York 14853, USA
    Nature 495:241-5. 2013
    ..We find that cells of the hilum OSE are cycling slowly and express stem and/or progenitor cell markers ALDH1, LGR5, LEF1, CD133 and CK6B...
  66. pmc Expansion of intestinal epithelial stem cells during murine development
    Jeffrey J Dehmer
    Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, United States of America
    PLoS ONE 6:e27070. 2011
    ..Actively cycling ISCs are labeled by Lgr5, Ascl2 and Olfm4; whereas slowly cycling or quiescent ISC are marked by Bmi1 and mTert...
  67. doi Characterization of Lgr5-positive epithelial cells in the murine thymus
    Eric Vroegindeweij
    Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
    Eur J Immunol 43:1243-51. 2013
    ..b>Lgr5 transcripts have also been detected in the developing murine thymus, leading to speculation that Lgr5 is a marker ..
  68. pmc Cdx2 determines the fate of postnatal intestinal endoderm
    Emma J Stringer
    Department of Biochemistry, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 7RH, UK
    Development 139:465-74. 2012
    ..Conditional inactivation of Cdx2 in adult intestinal epithelium, as well as specifically in the Lgr5-positive stem cells, of adult mice allows long-term survival of the animals but fails to produce this phenotype...
  69. pmc Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation
    Catherine H Wilson
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
    EMBO J 31:2486-97. 2012
    ..Thus NRBP1 is a conserved regulator of cell fate, that plays an important role in tumour suppression...
  70. pmc Skin squamous cell carcinoma propagating cells increase with tumour progression and invasiveness
    Gaelle Lapouge
    IRIBHM, Universite Libre de Bruxelles, Brussels, Belgium
    EMBO J 31:4563-75. 2012
    ..Our results illustrate the progressive increase of squamous skin TPCs with tumour progression and invasiveness and reveal that serial transplantation may be required to define the long-term renewal potential of TPCs...
  71. pmc CD24 can be used to isolate Lgr5+ putative colonic epithelial stem cells in mice
    Jeffrey B King
    Department of Medicine, University of North Carolina at Chapel Hill, USA
    Am J Physiol Gastrointest Liver Physiol 303:G443-52. 2012
    ..This pattern of distribution was similar to enhanced green fluorescent protein (EGFP) expression in Lgr5-EGFP mice...
  72. doi Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors
    Bon Kyoung Koo
    Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Nature 488:665-9. 2012
    b>LGR5+ stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals...
  73. pmc Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease
    Alan M Hanash
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Immunity 37:339-50. 2012
    ..Our findings reveal IL-22 as a critical regulator of tissue sensitivity to GVHD and a protective factor for ISCs during inflammatory intestinal damage...
  74. doi Developmental stage-specific contribution of LGR5(+) cells to basal and luminal epithelial lineages in the postnatal mammary gland
    Karin E de Visser
    Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Pathol 228:300-9. 2012
    The leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5 (LGR5) has been identified as a marker of cycling stem cells in several epithelial tissues, including small intestine, colon, stomach ..
  75. pmc Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis
    Matthew D Neal
    Division of Pediatric Surgery Children s Hospital of Pittsburgh and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA
    J Biol Chem 287:37296-308. 2012
    ..Using flow cytometry and fluorescent in situ hybridization for the intestinal stem cell marker Lgr5, we demonstrate that TLR4 is expressed on the Lgr5-positive intestinal stem cells...
  76. doi Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development
    Nick Barker
    Hubrecht Institute for Developmental Biology and Stem Cell Research University Medical Centre Utrecht, Utrecht, The Netherlands
    Cell Rep 2:540-52. 2012
    ..Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5(+ve) cells via in vivo lineage tracing...
  77. pmc Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation
    S Radulescu
    CR UK Beatson Institute of Cancer Research, Glasgow, UK
    Oncogene 32:2048-57. 2013
    ..Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach...
  78. doi Troy, a tumor necrosis factor receptor family member, interacts with lgr5 to inhibit wnt signaling in intestinal stem cells
    Bohumil Fafilek
    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Gastroenterology 144:381-91. 2013
    ..However, aberrant Wnt signaling leads to intestinal cancer. We investigated the roles of the Wnt pathway in homeostasis of the intestinal epithelium and during malignant transformation in human cells and mice...
  79. doi Cellular turnover in epithelial rests of Malassez in the periodontal ligament of the mouse molar
    Kyoko Oka
    Department of Anatomy, Nihon University School of Dentistry, Tokyo, Japan
    Eur J Oral Sci 120:484-94. 2012
    ..experiments and immunohistochemistry, using the stem-cell marker leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5). The results suggest that ERM clusters are maintained in the PDL, via cellular turnover, throughout life.
  80. pmc Restriction of intestinal stem cell expansion and the regenerative response by YAP
    Evan R Barry
    Stem Cell Program and Department of Hematology Oncology, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 493:106-10. 2013
    ..Additionally, our findings have important implications for the targeting of YAP in human malignancies...
  81. pmc Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea
    Renjie Chai
    Department of Otolaryngology Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 109:8167-72. 2012
    ..b>Lgr5, a Wnt target gene, marks distinct supporting cell types in the neonatal cochlea...
  82. ncbi Identification of a novel seven-transmembrane receptor with homology to glycoprotein receptors and its expression in the adult and developing mouse
    G Hermey
    Zentrum für Molekulare Neurobiologie, University of Hamburg, Martinistrasse 52, Hamburg, 20246, Germany
    Biochem Biophys Res Commun 254:273-9. 1999
    Using a PCR-based cloning strategy we have isolated a cDNA from mouse brain and named it fex, because it codes for a novel putative G protein-coupled receptor expressed in follicles...
  83. pmc Neonatal lethality of LGR5 null mice is associated with ankyloglossia and gastrointestinal distension
    Hiroki Morita
    Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
    Mol Cell Biol 24:9736-43. 2004
    The physiological role of an orphan G protein-coupled receptor, LGR5, was investigated by targeted deletion of this seven-transmembrane protein containing a large N-terminal extracellular domain with leucine-rich repeats...
  84. ncbi Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development
    Serge Nef
    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Switzerland
    Dev Biol 287:361-77. 2005
    ..These studies define the major characteristics of testicular and ovarian transcriptional programs and reveal the richness of signaling processes in differentiation of the bipotential gonads into testes and ovaries...
  85. doi A role for GATA-6 in vertebrate chondrogenesis
    Alexander Alexandrovich
    Division of Cardiovascular Medicine, King s College London, London SE5 9NU, UK
    Dev Biol 314:457-70. 2008
    ..We also show that the G-protein coupled receptor, Gpr49, is a target of GATA-6 regulation in differentiating embryonal carcinoma cells and that, in vivo, the expression ..
  86. pmc Genetic architecture of mouse skin inflammation and tumour susceptibility
    David A Quigley
    Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94115, USA
    Nature 458:505-8. 2009
    ..The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of the hair follicle, and the vitamin D receptor (Vdr) is linked to ..
  87. pmc Wnt signaling, lgr5, and stem cells in the intestine and skin
    Andrea Haegebarth
    Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The
    Am J Pathol 174:715-21. 2009
    ..The Wnt target gene Lgr5 has been recently identified as a novel stem cell marker of the intestinal epithelium and the hair follicle...
  88. doi Very long-term self-renewal of small intestine, colon, and hair follicles from cycling Lgr5+ve stem cells
    N Barker
    Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Cold Spring Harb Symp Quant Biol 73:351-6. 2008
    ..We have recently identified a novel stem cell gene Lgr5 expressed in multiple adult tissues...
  89. pmc In pursuit of leucine-rich repeat-containing G protein-coupled receptor-5 regulation and function in the uterus
    Xiaofei Sun
    Division of Reproductive Sciences, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
    Endocrinology 150:5065-73. 2009
    ..Because of this characteristic, we studied the status of Lgr5 expression in the mouse uterus under various conditions...
  90. doi Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt/beta-catenin signaling in the epithelial stem cells
    Marika Suomalainen
    Developmental Biology Programme, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Finland
    Dev Dyn 239:364-72. 2010
    ..Interestingly, these cells expressed specifically Lgr5, a Wnt target gene and stem cell marker in the intestine, suggesting that Lgr5 is a marker of incisor stem cells ..
  91. pmc Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis
    Wei Qiu
    University of Pittsburgh Cancer Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Proc Natl Acad Sci U S A 107:20027-32. 2010
    ..These results suggest that effective chemoprevention of colon cancer by NSAIDs lies in the elimination of stem cells that are inappropriately activated by oncogenic events through induction of apoptosis...
  92. pmc A stem cell marker-expressing subset of enteroendocrine cells resides at the crypt base in the small intestine
    Yoshitatsu Sei
    Gastroenterology Section, DDB, National Institute of Diabetes, Digestive and Kidney Diseases, 10 Center Dr, Bldg 10, Rm 9C 112, MSC1804, Bethesda, MD 20892 1385, USA
    Am J Physiol Gastrointest Liver Physiol 300:G345-56. 2011
    ..Further investigation of the function of this subset may provide novel insights into the genesis and development of enteroendocrine cells as well as enteroendocrine tumorigenesis...
  93. pmc Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium
    François Gerbe
    CNRS UMR5203, Montpellier F 34094, France
    J Cell Biol 192:767-80. 2011
    ..cells express DCLK1, a putative marker of quiescent stem cells, they are post-mitotic, short lived, derive from Lgr5-expressing epithelial stem cells, and are found in mouse and human tumors...
  94. pmc Notch signaling in stomach epithelial stem cell homeostasis
    Tae Hee Kim
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 208:677-88. 2011
    ..These results establish a role for Notch activity in the foregut and highlight the importance of cellular context in gastric tumorigenesis...
  95. pmc Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea
    Renjie Chai
    Department of Otolaryngology Head and Neck Surgery, Stanford University, CA 94305, USA
    J Assoc Res Otolaryngol 12:455-69. 2011
    ..b>Lgr5, a member of the G protein-coupled receptor family, is a Wnt target in the gastrointestinal and integumentary ..
  96. pmc Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury
    Andrei N Mardaryev
    Centre for Skin Sciences, School of Life Sciences, University of Bradford, UK
    Development 138:4843-52. 2011
    ..epithelial compartments (bulge, secondary hair germ) and co-express selected stem cell markers (Sox9, Tcf4 and Lgr5)...