Hans Clevers

Summary

Country: The Netherlands

Publications

  1. ncbi request reprint Wnt signaling: Ig-norrin the dogma
    Hans Clevers
    Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Curr Biol 14:R436-7. 2004
  2. ncbi request reprint Self-renewal and cancer of the gut: two sides of a coin
    Freddy Radtke
    Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Chemin de Boveresses 155, CH 1066 Epalinges, Switzerland
    Science 307:1904-9. 2005
  3. ncbi request reprint Wnt signaling in the intestinal epithelium: from endoderm to cancer
    Alex Gregorieff
    Netherlands Institute for Developmental Biology, Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands
    Genes Dev 19:877-90. 2005
  4. ncbi request reprint Wnt control of stem cells and differentiation in the intestinal epithelium
    Daniel Pinto
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands
    Exp Cell Res 306:357-63. 2005
  5. ncbi request reprint Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells
    Johan H van Es
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Nature 435:959-63. 2005
  6. ncbi request reprint At the crossroads of inflammation and cancer
    Hans Clevers
    Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands
    Cell 118:671-4. 2004
  7. ncbi request reprint Wnt breakers in colon cancer
    Hans Clevers
    Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands
    Cancer Cell 5:5-6. 2004
  8. ncbi request reprint Wnt/beta-catenin signaling in development and disease
    Hans Clevers
    Hubrecht Laboratory and Utrecht University, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands
    Cell 127:469-80. 2006
  9. doi request reprint The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium
    Alex Gregorieff
    Hubrecht Institute, Utrecht, The Netherlands
    Gastroenterology 137:1333-45.e1-3. 2009
  10. doi request reprint 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

Detail Information

Publications115 found, 100 shown here

  1. ncbi request reprint Wnt signaling: Ig-norrin the dogma
    Hans Clevers
    Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Curr Biol 14:R436-7. 2004
    ..Unexpectedly, a non-Wnt ligand for this receptor complex has now been discovered. This novel ligand, Norrin, is mutated in the hereditary ocular Norrie syndrome...
  2. ncbi request reprint Self-renewal and cancer of the gut: two sides of a coin
    Freddy Radtke
    Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Chemin de Boveresses 155, CH 1066 Epalinges, Switzerland
    Science 307:1904-9. 2005
    ..Here, we discuss the biology of the intestinal epithelium, emphasizing the roles played by Wnt, bone morphogenic protein, and Notch signaling cascades in epithelial self-renewal and cancer...
  3. ncbi request reprint Wnt signaling in the intestinal epithelium: from endoderm to cancer
    Alex Gregorieff
    Netherlands Institute for Developmental Biology, Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands
    Genes Dev 19:877-90. 2005
    ..In this review, we outline current understanding of the physiological role of Wnt signaling in intestinal biology. From this perspective, we then describe how mutational subversion of the Wnt cascade leads to colorectal cancer...
  4. ncbi request reprint Wnt control of stem cells and differentiation in the intestinal epithelium
    Daniel Pinto
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands
    Exp Cell Res 306:357-63. 2005
    ..We emphasize how Wnt signaling is able to maintain a stem cell/progenitor phenotype in normal intestinal crypts, and to impose a very similar phenotype onto colorectal adenomas...
  5. ncbi request reprint Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells
    Johan H van Es
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Nature 435:959-63. 2005
    ..Our data indicate that gamma-secretase inhibitors, developed for Alzheimer's disease, might be of therapeutic benefit in colorectal neoplastic disease...
  6. ncbi request reprint At the crossroads of inflammation and cancer
    Hans Clevers
    Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands
    Cell 118:671-4. 2004
    ..Two recent Cell (Greten et al., 2004; Rakoff-Nahoum et al., 2004) papers illuminate roles of Toll-like receptors and the NF-kappaB pathway in the control of epithelial homeostasis in health and disease...
  7. ncbi request reprint Wnt breakers in colon cancer
    Hans Clevers
    Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands
    Cancer Cell 5:5-6. 2004
    ..Ultimately, such inhibitors could become a novel class of smart anticancer drugs...
  8. ncbi request reprint Wnt/beta-catenin signaling in development and disease
    Hans Clevers
    Hubrecht Laboratory and Utrecht University, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands
    Cell 127:469-80. 2006
    ..Germline mutations in the Wnt pathway cause several hereditary diseases, and somatic mutations are associated with cancer of the intestine and a variety of other tissues...
  9. doi request reprint The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium
    Alex Gregorieff
    Hubrecht Institute, Utrecht, The Netherlands
    Gastroenterology 137:1333-45.e1-3. 2009
    ..In this study, we investigated the role of the Wnt-responsive, Ets-domain transcription factor Spdef in the differentiation of goblet and Paneth cells...
  10. doi request reprint 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
    ..The Lgr5(+) cells are intermingled with Paneth cells near the adenoma base, a pattern reminiscent of the architecture of the normal crypt niche...
  11. pmc T-cell factor 4 (Tcf7l2) maintains proliferative compartments in zebrafish intestine
    Vanesa Muncan
    Netherlands Institute for Developmental Biology, Center for Biomedical Research, Hubrecht Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
    EMBO Rep 8:966-73. 2007
    ..This study underscores the involvement of Tcf4 in maintaining proliferative self-renewal in the intestine throughout life...
  12. 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
    ..In colon crypts, CD24(+) cells residing between Lgr5 stem cells may represent the Paneth cell equivalents. We conclude that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell...
  13. ncbi request reprint 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
    ..The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers...
  14. ncbi request reprint EphB receptor activity suppresses colorectal cancer progression
    Eduard Batlle
    Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Nature 435:1126-30. 2005
    ..Our data demonstrate that loss of EphB expression represents a critical step in colorectal cancer progression...
  15. doi request reprint 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
    ..Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles. We conclude that Lgr6 marks the most primitive epidermal stem cell...
  16. pmc The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/β-catenin coactivators essential for intestinal homeostasis
    Tokameh Mahmoudi
    Hubrecht Institute and University Medical Centre Utrecht, Utrecht, The Netherlands
    PLoS Biol 8:e1000539. 2010
    ..The methyltransferase DOT1L may present an attractive candidate for drug targeting in colorectal cancer...
  17. doi request reprint 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 conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche...
  18. pmc Peyer's patch M cells derived from Lgr5(+) stem cells require SpiB and are induced by RankL in cultured "miniguts"
    Wim de Lau
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, and University Medical Centre Utrecht, Utrecht, The Netherlands
    Mol Cell Biol 32:3639-47. 2012
    ..We conclude that RankL-induced expression of SpiB is essential for Lgr5 stem cell-derived epithelial precursors to develop into M cells...
  19. ncbi request reprint 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
    ..We conclude that RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation...
  20. doi request reprint Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium
    Toshiro Sato
    Hubrecht Institute, KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands
    Gastroenterology 141:1762-72. 2011
    ..We have adapted the culture conditions to grow similar epithelial organoids from mouse colon and human small intestine and colon...
  21. pmc Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis
    Meritxell Huch
    Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Centre Utrecht, Utrecht, The Netherlands
    EMBO J 32:2708-21. 2013
    ..Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality. ..
  22. doi request reprint Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine
    Hugo J Snippert
    Hubrecht Institute, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
    Gastroenterology 136:2187-2194.e1. 2009
    ..To determine whether there is a relationship between these markers, we investigated the intestinal expression pattern of Prom1/CD133 and created knock-in mice to visualize and trace Prom1(+) cells...
  23. doi request reprint T-cell factor 4 (tcf7l2) is the main effector of Wnt signaling during zebrafish intestine organogenesis
    Ana Faro
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
    Zebrafish 6:59-68. 2009
    ..This study reveals that Tcf4 (tcf7l2) is the major effector of Wnt signaling in the intestine during zebrafish organogenesis...
  24. ncbi request reprint Wnt activates the Tak1/Nemo-like kinase pathway
    Linda Smit
    Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    J Biol Chem 279:17232-40. 2004
    ..Thus, Wnt signal transduction through the canonical pathway activates beta-catenin/TCF, whereas Wnt signal transduction through the Tak1 pathway phosphorylates and inhibits TCF, which might function as a feedback mechanism...
  25. pmc The kinase TNIK is an essential activator of Wnt target genes
    Tokameh Mahmoudi
    Hubrecht Institute KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands
    EMBO J 28:3329-40. 2009
    ..siRNA depletion of TNIK followed by expression array analysis showed that TNIK is an essential, specific activator of Wnt transcriptional programme. This kinase may present an attractive candidate for drug targeting in colorectal cancer...
  26. doi request reprint 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
    ..Quantitative analysis shows that stem cell turnover follows a pattern of neutral drift dynamics...
  27. ncbi request reprint The Intestinal Wnt/TCF Signature
    Laurens G van der Flier
    Hubrecht Institute, Netherlands Institute for Developmental Biology and Centre for Biomedical Genetics, Utrecht, The Netherlands
    Gastroenterology 132:628-32. 2007
    ..In colorectal cancer, activating mutations in the Wnt pathway transform epithelial cells through the inappropriate expression of a TCF4 target gene program, which is physiologically expressed in intestinal crypts...
  28. ncbi request reprint Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB
    Eduard Batlle
    Department of Immunology and Center for Biomedical Genetics, University Medical Center, Utrecht, The Netherlands
    Cell 111:251-63. 2002
    ..We conclude that in the intestinal epithelium beta-catenin and TCF couple proliferation and differentiation to the sorting of cell populations through the EphB/ephrin-B system...
  29. ncbi request reprint Many inflammatory bowel disease risk loci include regions that regulate gene expression in immune cells and the intestinal epithelium
    Michal Mokry
    Division of Pediatrics, Wilhelmina Children s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
    Gastroenterology 146:1040-7. 2014
    ..These studies have focused mainly on protein-coding genes. We investigated other functional elements in the human genome, such as regulatory regions...
  30. ncbi request reprint 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
    ..These findings establish a novel paradigm for stem-cell maintenance in which a dynamically heterogeneous cell population is able to function long term as a single stem-cell pool...
  31. ncbi request reprint The Wnt/beta-catenin pathway regulates cardiac valve formation
    Adam F L Hurlstone
    Netherlands Institute for Developmental Biology, Hubrecht Laboratory and Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
    Nature 425:633-7. 2003
    ..Our findings identify a novel role for Wnt/beta-catenin signalling in determining endocardial cell fate...
  32. doi request reprint Intestinal regeneration: YAP-tumor suppressor and oncoprotein?
    Vivian S W Li
    Hubrecht Institute KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Curr Biol 23:R110-2. 2013
    ..A recent study paradoxically reports that genetic removal of YAP enhances intestinal stem cell expansion and regeneration...
  33. doi request reprint Controlled gene expression in primary Lgr5 organoid cultures
    Bon Kyoung Koo
    Hubrecht Institute for Developmental Biology and Stem Cell Research, and University Medical Centre, Utrecht, The Netherlands
    Nat Methods 9:81-3. 2012
    ..We present here a method based on Cre recombinase-inducible retrovirus vectors that allows the conditional manipulation of gene expression in primary mouse organoid culture systems...
  34. pmc Hindgut defects and transformation of the gastro-intestinal tract in Tcf4(-/-)/Tcf1(-/-) embryos
    Alex Gregorieff
    Netherlands Institute for Developmental Biology and Center for Biomedical Genetics, Hubrecht Laboratory, Uppsalalaan, CT Utrecht, The Netherlands
    EMBO J 23:1825-33. 2004
    ..Our results reveal a novel role for Wnt signalling in early gut morphogenesis and suggest that specific Wnt-driven patterning events are determined by the unique tissue distribution of Tcf/Lef family members...
  35. doi request reprint Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex
    Jean Paul ten Klooster
    Hubrecht Institute, KNAW and University Medical Centre, Utrecht, The Netherlands
    Dev Cell 16:551-62. 2009
    ..These data define a brush border induction pathway downstream of the Lkb1/Strad/Mo25 polarization complex, yet separate from other polarity events...
  36. pmc Efficient double fragmentation ChIP-seq provides nucleotide resolution protein-DNA binding profiles
    Michal Mokry
    Cancer Genomics Center, Department of Medical Genetics, Hubrecht Institute and University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 5:e15092. 2010
    ..Although optimized for the AB/SOLiD platform, the same approach may be applied to other platforms...
  37. ncbi request reprint Wnt signalling induces maturation of Paneth cells in intestinal crypts
    Johan H van Es
    Hubrecht Institute, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Nat Cell Biol 7:381-6. 2005
    ..These observations imply that Wnt signals in the crypt can separately drive a stem-cell/progenitor gene programme and a Paneth-cell maturation programme. In intestinal cancer, both gene programmes are activated simultaneously...
  38. ncbi request reprint De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine
    Anna Pavlina G Haramis
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, Netherlands
    Science 303:1684-6. 2004
    ..Many JP cases are known to harbor mutations in BMP pathway genes. These data indicate that intestinal BMP signaling represses de novo crypt formation and polyp growth...
  39. ncbi request reprint Expression pattern of Wnt signaling components in the adult intestine
    Alex Gregorieff
    Netherlands Institute for Developmental Biology and Center for Biomedical Genetics, Hubrecht Laboratory, Utrecht
    Gastroenterology 129:626-38. 2005
    ..To address this issue, we examined the expression pattern of all Wnts, Frizzleds (Fzs), low-density lipoprotein receptor-related proteins, Wnt antagonists, and T-cell factors in the murine small intestine and colon and adenomas...
  40. pmc Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells
    Pantelis Hatzis
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Mol Cell Biol 28:2732-44. 2008
    ..The TCF4-binding regions significantly correlate with Wnt-responsive gene expression profiles derived from primary human adenomas and often behave as beta-catenin/TCF4-dependent enhancers in transient reporter assays...
  41. 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
    ..This review attempts to provide a comprehensive overview of the stem cell compartments in the intestine and skin with a focus on the cycling, yet long-lived and multipotent, Lgr5(+ve) stem cell populations...
  42. doi request reprint Generation of L cells in mouse and human small intestine organoids
    Natalia Petersen
    Hubrecht Institute KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands
    Diabetes 63:410-20. 2014
    ..Thus, our platform allows us to study and modulate the development of L cells in mouse and human crypts as a potential basis for novel therapeutic strategies in patients with type 2 diabetes. ..
  43. doi request reprint 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
    ....
  44. pmc Integrated genome-wide analysis of transcription factor occupancy, RNA polymerase II binding and steady-state RNA levels identify differentially regulated functional gene classes
    Michal Mokry
    Hubrecht Institute KNAW and University Medical Center, 3584 CT Utrecht, The Netherlands
    Nucleic Acids Res 40:148-58. 2012
    ..These categories are strongly enriched for genes from different functional classes. Our results demonstrate a complementary value in Pol II chip-seq and RNA-seq approaches for better understanding of gene expression regulation...
  45. doi request reprint Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells
    Nick Barker
    Hubrecht Institute, Uppsalalaan, Utrecht, The Netherlands
    Gastroenterology 138:1681-96. 2010
    ..Further studies of these markers might reveal adult stem cell populations in additional tissues. Identification of the ligands for Lgr5 and 6 will help elucidate stem cell functions and modes of intracellular signaling...
  46. pmc Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc
    Vanesa Muncan
    Hubrecht Laboratory, Nederlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Mol Cell Biol 26:8418-26. 2006
    ..c-Myc appears essential for crypt progenitor cells to provide the necessary biosynthetic capacity to successfully progress through the cell cycle...
  47. ncbi request reprint Stem cells, self-renewal, and differentiation in the intestinal epithelium
    Laurens G van der Flier
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands
    Annu Rev Physiol 71:241-60. 2009
    ..These studies describe a genetic hierarchy responsible for cell fate commitment in normal gut physiology. Where relevant we also mention aberrant deregulation of these molecular pathways that results in colon cancer...
  48. ncbi request reprint Live and let die in the intestinal epithelium
    Elena Sancho
    Centre for Biomedical Genetics, Hubrecht Laboratorium, Koninklijke Nederlandse Akademie van Wetenschappen, Utrecht, The Netherlands
    Curr Opin Cell Biol 15:763-70. 2003
    ..Wnt signalling appears to control most of these events...
  49. pmc Canonical Wnt signals are essential for homeostasis of the intestinal epithelium
    Daniel Pinto
    Netherlands Institute for Developmental Biology, Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Genes Dev 17:1709-13. 2003
    ..Thus, our data are the first to establish a direct requirement for Wnt ligands in driving proliferation in the intestinal epithelium, and also define an unexpected role for Wnts in controlling secretory cell differentiation...
  50. pmc Specific inhibition of gene expression using a stably integrated, inducible small-interfering-RNA vector
    Marc van de Wetering
    Hubrecht Laboratory, Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    EMBO Rep 4:609-15. 2003
    ..The inhibition of two other genes using this vector system shows that it should be useful for the inducible knockdown of gene expression...
  51. doi request reprint Wnt-induced transcriptional activation is exclusively mediated by TCF/LEF
    Jurian Schuijers
    Hubrecht Institute KNAW, University Medical Centre Utrecht, Utrecht, The Netherlands
    EMBO J 33:146-56. 2014
    ..Our results indicate that β-catenin is tethered to chromatin overwhelmingly through the TCF/LEF transcription factors in these three systems. ..
  52. doi request reprint Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells
    Henner F Farin
    Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Utrecht, The Netherlands
    Gastroenterology 143:1518-1529.e7. 2012
    ..Paneth cells support stem cells by secreting Wnt, but little is known about the exact sources and primary functions of individual Wnt family members...
  53. doi request reprint MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway
    Ser Sue Ng
    Hubrecht Institute, KNAW and University Medical Centre Utrecht, Uppsalalaan 8, NL 3584 CT Utrecht, The Netherlands
    Biol Chem 391:171-80. 2010
    ..These results suggest that MAP3K1, previously reported as an Axin1 inter-actor in c-Jun NH(2)-terminal kinase pathway, is also involved in the canonical Wnt signalling pathway and positively regulates expression of Wnt target genes...
  54. ncbi request reprint Wnt, stem cells and cancer in the intestine
    Daniel Pinto
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands
    Biol Cell 97:185-96. 2005
    ....
  55. ncbi request reprint Caught up in a Wnt storm: Wnt signaling in cancer
    Rachel H Giles
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
    Biochim Biophys Acta 1653:1-24. 2003
    ....
  56. doi request reprint Fishing for intestinal cancer models: unraveling gastrointestinal homeostasis and tumorigenesis in zebrafish
    Ana Faro
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
    Zebrafish 6:361-76. 2009
    ..An appealing avenue for cancer research in zebrafish is large-scale screens to identify chemotherapeutic and chemopreventive agents in conjunction with the in vivo imaging approaches that zebrafish affords...
  57. ncbi request reprint Thymocyte development: drama without Brahma
    Hans Clevers
    Hubrecht Laboratory, Center for Biomedical Genetics, Utrecht, The Netherlands
    Immunity 19:157-8. 2003
  58. ncbi request reprint The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength
    Wim de Lau
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences KNAW, University Medical Centre Utrecht, 3584 CT Utrecht, The Netherlands
    Genes Dev 28:305-16. 2014
    ..Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists. ..
  59. doi request reprint Differentiated human colorectal cancer cells protect tumor-initiating cells from irinotecan
    Benjamin L Emmink
    Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
    Gastroenterology 141:269-78. 2011
    ..We studied the relationship between resistance to the topoisomerase I inhibitor irinotecan and tumor-initiating potential in human colonosphere cultures and in mice with colorectal xenograft tumors...
  60. pmc Tracking adult stem cells
    Hugo J Snippert
    Hubrecht Institute, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
    EMBO Rep 12:113-22. 2011
    ..An accurate interpretation of physiologically relevant stem-cell assays is crucial to identify adult stem cells and elucidate how they self-renew and give rise to differentiated progeny...
  61. pmc Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes
    Arnout G Schepers
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
    EMBO J 30:1104-9. 2011
    ..We determined the average cell cycle length of Lgr5+ve stem cells at 21.5 h and find that Lgr5+ve intestinal stem cells randomly segregate newly synthesized DNA strands, opposing the 'immortal strand' hypothesis...
  62. ncbi request reprint WNT signaling in the normal intestine and colorectal cancer
    Wim de Lau
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands
    Front Biosci 12:471-91. 2007
    ..The Eph/Ephrin system also operates to limit progression of colorectal cancer beyond the early stages...
  63. ncbi request reprint AU-rich elements and alternative splicing in the beta-catenin 3'UTR can influence the human beta-catenin mRNA stability
    Andrea Thiele
    Hubrecht Laboratory, The Netherlands Institute of Developmental Biology, Uppsalalaan 8, NL 3584 CT Utrecht, The Netherlands
    Exp Cell Res 312:2367-78. 2006
    ..These results suggest that alternative splicing and AREs can act together in regulating beta-catenin mRNA stability and thereby provide a step of controlling the cellular beta-catenin concentration...
  64. ncbi request reprint TCF: Lady Justice casting the final verdict on the outcome of Wnt signalling
    Helen Brantjes
    Department of Immunology, University Hospital Utrecht, The Netherlands
    Biol Chem 383:255-61. 2002
    ..In the absence of Wnt signalling, Tcf complexes with several transcriptional repressor proteins ensuring active repression of Tcf target genes. In this review the dual role of Tcf proteins in the Wnt signalling cascade will be discussed...
  65. ncbi request reprint Signaling mucins in the (S)limelight
    Hans Clevers
    Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands
    Dev Cell 7:150-1. 2004
    ..In a recent issue of Genes & Development, Cullen et al. show that the C terminus of membrane mucin-like Msb2 activates a CDC42/MAPK cascade to control filamentous growth of baker's yeast...
  66. doi request reprint Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex
    Vivian S W Li
    Hubrecht Institute, KNAW and University Medical Centre Utrecht, The Netherlands
    Cell 149:1245-56. 2012
    ..Subsequently, newly synthesized β-catenin can accumulate in a free cytosolic form and engage nuclear TCF transcription factors...
  67. doi request reprint In situ hybridization to identify gut stem cells
    Alex Gregorieff
    Hubrecht Institute, Utrecht, The Netherlands
    Curr Protoc Stem Cell Biol . 2010
    ..This methodology allows researchers to quickly visualize the expression profile of putative stem cell markers with a high degree of sensitivity and resolution...
  68. ncbi request reprint Notch and Wnt inhibitors as potential new drugs for intestinal neoplastic disease
    Johan H van Es
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Trends Mol Med 11:496-502. 2005
    ..We focus on the potential of recently identified small-molecule inhibitors of the Wnt pathway and gamma-secretase inhibitors of the Notch pathway as novel colon cancer therapeutics...
  69. ncbi request reprint Inflating cell numbers by Wnt
    Hans Clevers
    Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands
    Mol Cell 10:1260-1. 2002
    ..As a downstream target gene of the Wnt cascade, the bicoid-related transcription factor Pitx2 directly drives proliferation in these tissues...
  70. ncbi request reprint The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells
    Marc van de Wetering
    Department of Immunology and Center for Biomedical Genetics, University Medical Center, 3584 CX, Utrecht, The Netherlands
    Cell 111:241-50. 2002
    ..Thus, the beta-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells...
  71. pmc The intestinal stem cell
    Nick Barker
    Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Genes Dev 22:1856-64. 2008
    ..This review attempts to provide a comprehensive overview of four decades of research on crypt stem cells...
  72. pmc Giving APCmin tumours a SPARC
    Alex Gregorieff
    Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Gut 56:1341-3. 2007
  73. ncbi request reprint LKB1 tumor suppressor protein: PARtaker in cell polarity
    Annette F Baas
    Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Trends Cell Biol 14:312-9. 2004
    ..In this article, we summarize the findings regarding LKB1 over the past six years. In addition, we discuss LKB1 in polarity in the context of both the other PAR proteins and its tumor suppressive activities...
  74. ncbi request reprint Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiency
    Ronald C J Gallagher
    Department of Biomedical Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG, UK
    Oncogene 21:6446-57. 2002
    ..However, additional deficiency of Tcf-1 completely blocks normal mammary development and results in acanthoma...
  75. ncbi request reprint Notch1 functions as a tumor suppressor in mouse skin
    Michael Nicolas
    Ludwig Institute for Cancer Research, Lausanne Branch, University Lausanne, 1066 Epalinges, Switzerland
    Nat Genet 33:416-21. 2003
    ..This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin...
  76. pmc Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors
    Barbara Lustig
    Max Delbrueck Center for Molecular Medicine, D 13092 Berlin, Germany
    Mol Cell Biol 22:1184-93. 2002
    ..These results demonstrate that conductin is a target of the Wnt signaling pathway. Upregulation of conductin may constitute a negative feedback loop that controls Wnt signaling activity...
  77. doi request reprint Tissue-resident adult stem cell populations of rapidly self-renewing organs
    Nick Barker
    Hubrecht Institute, Utrecht, The Netherlands
    Cell Stem Cell 7:656-70. 2010
    ..Here, we review recent advances in adult stem cell biology, highlighting the promise and pitfalls of the candidate biomarkers of the various stem cell populations...
  78. ncbi request reprint EphB/EphrinB receptors and Wnt signaling in colorectal cancer
    Hans Clevers
    Hubrecht Laboratory and Centre for Biomedical Genetics, Utrecht, The Netherlands
    Cancer Res 66:2-5. 2006
    ..Here, we review the current knowledge of the EphB/ephrinB system in the intestinal epithelium and we discuss their tumor suppressor role in the context of the multistep progression of colorectal cancer...
  79. doi request reprint Lineage tracing in the intestinal epithelium
    Nick Barker
    Hubrecht Institute for Developmental Biology and Stem Cell Research, and University Medical Center Utrecht UMCU, Utrecht, The Netherlands
    Curr Protoc Stem Cell Biol . 2010
    ..The same protocols can be applied to performing in vivo lineage tracing from other Lgr5(+ve) stem cell populations, including those in the hair-follicle and stomach...
  80. doi request reprint Stem cells and cancer of the stomach and intestine
    Robert G J Vries
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, Utrecht, Netherlands
    Mol Oncol 4:373-84. 2010
    ..Therefore, these models represent two sides of the same coin...
  81. ncbi request reprint You Wnt some, you lose some: oncogenes in the Wnt signaling pathway
    Johan H van Es
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands
    Curr Opin Genet Dev 13:28-33. 2003
    ..Collectively, this represents an important step forward in our understanding of the role of Wnt signaling in development and oncogenesis...
  82. pmc SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes
    Philippe Blache
    Institut de Genetique Humaine, CNRS UPR1142, 141 rue de la Cardonille, 34396 Montpellier, Cedex 5, France
    J Cell Biol 166:37-47. 2004
    ....
  83. ncbi request reprint Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation
    Donald A Glass
    Department of Molecular and Human Genetics, Bone Disease Program of Texas, Houston, 77030, USA
    Dev Cell 8:751-64. 2005
    ....
  84. pmc Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration
    Owen J Sansom
    School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales
    Genes Dev 18:1385-90. 2004
    ..Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting...
  85. ncbi request reprint Identification of two novel regulated serines in the N terminus of beta-catenin
    Mascha van Noort
    Department of Immunology, University Medical Center Utrecht, The Netherlands
    Exp Cell Res 276:264-72. 2002
    ..During embryogenesis, the phosphorylation status of S23 and S29 appears to be actively regulated. Nevertheless, constructs harboring the mutations found in tumors fail to show enhanced transcriptional activity or transforming properties...
  86. ncbi request reprint Aberrant polycystin-1 expression results in modification of activator protein-1 activity, whereas Wnt signaling remains unaffected
    Ngoc Hang Le
    Department of Human Genetics, Leiden University Medical Center, Leiden 2333 AL, The Netherlands
    J Biol Chem 279:27472-81. 2004
    ..Since our data indicate that aberrant polycystin-1 expression results in altered AP-1 activity, polycystin-1 may be required for adequate AP-1 activity...
  87. ncbi request reprint TCF transcription factors, mediators of Wnt-signaling in development and cancer
    Mascha van Noort
    Department of Immunology, UMC Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands
    Dev Biol 244:1-8. 2002
  88. ncbi request reprint Mining the Wnt pathway for cancer therapeutics
    Nick Barker
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8 3584CT, Utrecht, The Netherlands
    Nat Rev Drug Discov 5:997-1014. 2006
    ..Here we provide an overview of the promise and pitfalls of current drug development strategies striving to inhibit the Wnt pathway and present new opportunities for therapeutic intervention...
  89. ncbi request reprint Tracking down the stem cells of the intestine: strategies to identify adult stem cells
    Nick Barker
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
    Gastroenterology 133:1755-60. 2007
  90. ncbi request reprint Colon cancer--understanding how NSAIDs work
    Hans Clevers
    Netherlands Institute for Developmental Biology, Utrecht, The Netherlands
    N Engl J Med 354:761-3. 2006
  91. doi request reprint LKB1 and AMPK family signaling: the intimate link between cell polarity and energy metabolism
    Marnix Jansen
    Hubrecht Institute, Developmental Biology and Stem Cell Research, 3584 CT Utrecht, The Netherlands
    Physiol Rev 89:777-98. 2009
    ..Elucidation of the molecular mechanism responsible for Peutz-Jeghers syndrome will undoubtedly reveal important insight into cancer development in the larger population...
  92. pmc Illegitimate WNT signaling promotes proliferation of multiple myeloma cells
    Patrick W B Derksen
    Department of Pathology, Academic Medical Center, University of Amsterdam, 1105AZ, Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 101:6122-7. 2004
    ..We therefore suggest that MM cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer...
  93. ncbi request reprint Beta-catenin regulates Cripto- and Wnt3-dependent gene expression programs in mouse axis and mesoderm formation
    Markus Morkel
    Max Delbrueck Center for Molecular Medicine, Robert Roessle Strasse 10, 13125 Berlin, Germany
    Development 130:6283-94. 2003
    ..Our data assign a key role to beta-catenin upstream of two distinct gene expression programs during anteroposterior axis and mesoderm formation...
  94. ncbi request reprint Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine
    Owen J Sansom
    School of Biosciences, University of Cardiff, Museum P O Box 911, Cardiff CF103US, Wales, United Kingdom
    J Biol Chem 280:28463-7. 2005
    ..Taken together, this argues that cyclin D1 up-regulation in intestinal neoplasia is important for tumor progression rather than initiation...
  95. ncbi request reprint WNT signaling and lymphocyte development
    Marc van de Wetering
    Department of Immunology, UMC Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
    Cell 109:S13-9. 2002
    ..Recent data indicate that at least two of these, the Wnt and the Notch cascades, have been recruited by the vertebrate immune system to control early lymphopoiesis...
  96. ncbi request reprint Wnt signaling controls the phosphorylation status of beta-catenin
    Mascha van Noort
    Department of Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
    J Biol Chem 277:17901-5. 2002
    ..Immunohistochemical analysis of mouse embryos utilizing the antibody visualizes sites that transduce Wnt signals through the canonical Wnt cascade...
  97. doi request reprint Slide preparation for single-cell-resolution imaging of fluorescent proteins in their three-dimensional near-native environment
    Hugo J Snippert
    Hubrecht Institute KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
    Nat Protoc 6:1221-8. 2011
    ..Generation of near-native sections ready for imaging analysis takes approximately 2-3 h. Postsectioning processes, such as antibody labeling or EdU detection, take up to 10 h...
  98. pmc Cloning and characterization of hELD/OSA1, a novel BRG1 interacting protein
    Adam F L Hurlstone
    University Medical Centre Utrecht, Department of Immunology, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
    Biochem J 364:255-64. 2002
    ..EHD1 and EHD2 also appear capable of interacting with each other. Using an antibody raised against EHD2 of hELD/OSA1, we detected Eld/Osa1 in endogenous SWI/SNF complexes derived from mouse brain...
  99. ncbi request reprint Survivin and molecular pathogenesis of colorectal cancer
    Paul J Kim
    Department of Cancer Biology and the Cancer Center, University of Massachusetts, Medical School, Worcester, MA, USA
    Lancet 362:205-9. 2003
    ..Survivin is a bifunctional regulator of cell death and cell proliferation expressed during embryonic development but undetectable in healthy adult tissues and re-expressed in many cancers, including colorectal cancer...
  100. ncbi request reprint TCF and Groucho-related genes influence pituitary growth and development
    Michelle L Brinkmeier
    Department of Human Genetics, University of Michigan Medical School, 4301 MSRBIII, Ann Arbor, Michigan 48109 0638, USA
    Mol Endocrinol 17:2152-61. 2003
    ..Thus, we demonstrate that Tcf4 and Aes influence pituitary growth and development, and place Tcf4 and Tle3 in the genetic hierarchy with Prop1...
  101. ncbi request reprint Armadillo/beta-catenin signals in the nucleus--proof beyond a reasonable doubt?
    Mariann Bienz
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Nat Cell Biol 5:179-82. 2003
    ..Plausible explanations allow these observations to be reconciled with the large body of evidence supporting a nuclear function of Arm/beta-catenin...