Research Topics
Genomes and Genes
| Konrad HochedlingerSummaryAffiliation: Harvard University Country: USA Publications
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Detail Information
Publications
Embryonic stem cells: testing the germ-cell theoryKonrad Hochedlinger
Howard Hughes Medical Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
Curr Biol 21:R850-2. 2011..The exact cellular origin of embryonic stem cells remains elusive. Now a new study provides compelling evidence that embryonic stem cells, established under conventional culture conditions, originate from a transient germ-cell state...
Epigenetic reprogramming and induced pluripotencyKonrad Hochedlinger
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Boston, MA 02114, USA
Development 136:509-23. 2009..Moreover, iPS cells can teach us about principles of normal development and disease, and might ultimately facilitate the treatment of patients by custom-tailored cell therapy...
Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cellsSarah Eminli
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, Massachusetts, USA
Nat Genet 41:968-76. 2009..Moreover, we identify hematopoietic progenitors as an attractive cell type for applications of iPS cell technology in research and therapy...
Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cellsJose M Polo
Howard Hughes Medical Institute and Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, Cambridge, Massachusetts, USA
Nat Biotechnol 28:848-55. 2010..These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages...
Induced pluripotent stem cells generated without viral integrationMatthias Stadtfeld
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA
Science 322:945-9. 2008..Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells...
Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of miceKatrin 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...
Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cellsJochen Utikal
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Massachusetts General Hospital Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA
J Cell Sci 122:3502-10. 2009..In addition, our results suggest that cancer cells remain susceptible to transcription factor-mediated reprogramming, which should facilitate the study of epigenetic changes in human cancer...
Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cellsAdlen Foudi
Cancer Center, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Nat Biotechnol 27:84-90. 2009..8-1.8% per day)...
ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishableTobias Brambrink
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Proc Natl Acad Sci U S A 103:933-8. 2006..Our findings support the notion that ES cell lines derived from cloned or fertilized blastocysts have an identical therapeutic potential...
Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissuesKonrad Hochedlinger
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Cell 121:465-77. 2005..These data show that certain adult progenitors remain competent to interpret key embryonic signals and support the notion that progenitor cells are a driving force in tumorigenesis...
In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like stateMarius Wernig
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
Nature 448:318-24. 2007..Our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells...
Nuclear cloning of embryonal carcinoma cellsRobert H Blelloch
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Proc Natl Acad Sci U S A 101:13985-90. 2004..Our findings support the notion that cancer results from the deregulation of stem cells and further suggest that the genetics of ECs will reveal genes involved in stem cell self-renewal and pluripotency...
Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cellsCaroline Beard
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
Genesis 44:23-8. 2006..This strategy and the vectors described here are generally applicable to any locus in ES cells and should allow for the rapid production of mice with transgenes efficiently targeted to a defined site...
Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cellsMatthias Stadtfeld
Massachusetts General Hospital Center for Regenerative Medicine, Harvard Stem Cell Institute, Boston, Massachusetts, USA
Nat Genet 44:398-405, S1-2. 2012..More generally, these findings indicate that culture conditions during cellular reprogramming can strongly influence the epigenetic and biological properties of the resultant iPSCs...
Cross-regulation of the Nanog and Cdx2 promotersLingyi Chen
Division of Pediatric Hematology Oncology, Children s Hospital Boston, Dana Farber Cancer Institute, Boston, MA, USA
Cell Res 19:1052-61. 2009..However, whereas Nanog knockout results in detectable Cdx2 expression in the ICM, we observe no overt disruption of blastocyst development, indicating that Nanog plays a subservient role to Oct4 in segregation of the ICM and TE...
Reprogramming of neural progenitor cells into induced pluripotent stem cells in the absence of exogenous Sox2 expressionSarah Eminli
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, Massachusetts 02114, USA
Stem Cells 26:2467-74. 2008..These results also imply that the combination of factors necessary for reprogramming is dependent on cellular context. Disclosure of potential conflicts of interest is found at the end of this article...
Guidelines and techniques for the generation of induced pluripotent stem cellsNimet Maherali
Massachusetts General Hospital Center for Regenerative Medicine and Cancer Center, Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, 185 Cambridge Street, Boston, MA 02114, USA
Cell Stem Cell 3:595-605. 2008..In addition, specific procedures aimed to optimize reproducible iPSC derivation are presented, with an emphasis on standardization of certain parameters for accurate comparison between independent experiments...
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cellsMatthias Stadtfeld
Howard Hughes Medical Institute at Massachusetts General Hospital, Center for Regenerative Medicine Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Nature 465:175-81. 2010..Thus, the expression state of a single imprinted gene cluster seems to distinguish most murine iPSCs from ES cells and allows for the prospective identification of iPSC clones that have the full development potential of ES cells...
Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contributionNimet Maherali
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, MA 02114, USA
Cell Stem Cell 1:55-70. 2007....
A high-efficiency system for the generation and study of human induced pluripotent stem cellsNimet Maherali
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Massachusetts General Hospital Center for Regenerative Medicine, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
Cell Stem Cell 3:340-5. 2008..The ability to reprogram cells at high efficiency provides a unique platform to dissect the underlying molecular and biochemical processes that accompany nuclear reprogramming...
A reprogrammable mouse strain from gene-targeted embryonic stem cellsMatthias Stadtfeld
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, Boston, Massachusetts, USA
Nat Methods 7:53-5. 2010..As these 'reprogrammable mice' can be easily bred, they are a useful tool to study the mechanisms underlying cellular reprogramming...
Immortalization eliminates a roadblock during cellular reprogramming into iPS cellsJochen Utikal
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Nature 460:1145-8. 2009..Our results show that the acquisition of immortality is a crucial and rate-limiting step towards the establishment of a pluripotent state in somatic cells and underscore the similarities between induced pluripotency and tumorigenesis...
Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouseMatthias Stadtfeld
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA
Cell Stem Cell 2:230-40. 2008..Our results suggest that factor-induced reprogramming is a gradual process with defined intermediate cell populations that contain the majority of cells poised to become iPS cells...
Oct4 expression is not required for mouse somatic stem cell self-renewalChristopher J Lengner
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
Cell Stem Cell 1:403-15. 2007..Oct4 gene ablation in these tissues revealed no abnormalities in homeostasis or regenerative capacity. We conclude that Oct4 is dispensable for both self-renewal and maintenance of somatic stem cells in the adult mammal...
Reprogramming of pancreatic beta cells into induced pluripotent stem cellsMatthias Stadtfeld
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA
Curr Biol 18:890-4. 2008..Our results provide genetic proof that terminally differentiated cells can be reprogrammed into pluripotent cells, suggesting that in vitro reprogramming is not restricted to certain cell types or differentiation stages...
X chromosome choice occurs independently of asynchronous replication timingJoost Gribnau
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
J Cell Biol 168:365-73. 2005....
Disease-specific induced pluripotent stem cellsIn Hyun Park
Department of Medicine, Division of Pediatric Hematology Oncology, Children s Hospital Boston, and Dana Farber Cancer Institute, Boston, MA 02115, USA
Cell 134:877-86. 2008..Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development...
Nuclear cloning, epigenetic reprogramming and cellular differentiationRudolf Jaenisch
Whitehead Institute, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
Novartis Found Symp 265:107-18; discussion 118-28. 2005..Finally, we discuss our recent studies on the reprogramming of nuclei from terminally differentiated neurons and from cancer cells...
A molecular roadmap of reprogramming somatic cells into iPS cellsJose M Polo
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA
Cell 151:1617-32. 2012..Collectively, our data offer new mechanistic insights into the nature and sequence of molecular events inherent to cellular reprogramming...
Nuclear reprogramming and pluripotencyKonrad Hochedlinger
Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 441:1061-7. 2006..The future challenge will be to study alternatives to nuclear transfer in order to recapitulate reprogramming in a Petri dish without the use of oocytes...
Induced pluripotency: history, mechanisms, and applicationsMatthias Stadtfeld
Howard Hughes Medical Institute, Harvard University and Harvard Medical School, Cambridge, Massachusetts 02138, USA
Genes Dev 24:2239-63. 2010..In this review, we summarize the progress that has been made in the iPSC field over the last 4 years, with an emphasis on understanding the mechanisms of cellular reprogramming and its potential applications in cell therapy...
Reprogramming of a melanoma genome by nuclear transplantationKonrad Hochedlinger
Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
Genes Dev 18:1875-85. 2004..Our findings serve as a paradigm for studying the tumorigenic effect of a given cancer genome in the context of a whole animal...
A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cellsChrista Buecker
Center for Regenerative Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
Cell Stem Cell 6:535-46. 2010..Finally, we demonstrate that the hLR5 state facilitates gene targeting, and as such provides a powerful tool for the generation of recombinant human pluripotent stem cell lines...
Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMycNimet Maherali
Massachusetts General Hospital Center for Regenerative Medicine, Harvard Stem Cell Institute, Boston, 02114, USA
Curr Biol 19:1718-23. 2009..The identification of a highly characterized pathway operating in iPSC induction will open new avenues for mechanistic dissection of the reprogramming process...
gPS navigates germ cells to pluripotencyNiels Geijsen
Massachusetts General Hospital Center for Regenerative Medicine and Cancer Center, Harvard Stem Cell Institute, Boston, MA 02114, USA
Cell Stem Cell 5:3-4. 2009..In this issue of Cell Stem Cell, Ko et al. (2009) reproducibly generate pluripotent cell lines from murine testes and unequivocally demonstrate their origin from spermatogonial stem cells...
T-cell receptor-driven lymphomagenesis in mice derived from a reprogrammed T cellThomas Serwold
Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 107:18939-43. 2010....
Chromatin connections to pluripotency and cellular reprogrammingStuart H Orkin
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
Cell 145:835-50. 2011..Manipulation of cell state through the process of transdifferentiation suggests that environmental cues may direct transcriptional programs as cells enter a transiently "plastic" state during reprogramming...
Direct in vivo VH to JH rearrangement violating the 12/23 ruleSergei B Koralov
The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 201:341-8. 2005..There is no preferential usage of any particular VH gene family or JH element in VHJH junctions, indicating that 23/23-guided recombination is possible, but is a low frequency event at the IgH locus in vivo...
The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early developmentJinzhong Qin
Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
Cell Stem Cell 11:319-32. 2012..However, some developmental regulators are repressed by the combined activity of all three complexes. Together, we have uncovered a highly selective, essential role for an atypical PRC1-family complex in ES cells and early development...
The sox family of transcription factors: versatile regulators of stem and progenitor cell fateAbby Sarkar
Howard Hughes Medical Institute at Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA
Cell Stem Cell 12:15-30. 2013..Here, we review molecular and functional evidence linking Sox proteins with stem cell biology, cellular reprogramming, and disease with an emphasis on Sox2...
Nuclear transplantation, embryonic stem cells and the potential for cell therapyKonrad Hochedlinger
Whitehead Institute, Cambridge, MA, USA
Hematol J 5:S114-7. 2004..Moreover, we will discuss the potential use of nuclear transfer to study the role of reversible genomic (epigenetic) modifications during tumorigenesis...
A gutsy way to grow: intestinal stem cells as nutrient sensorsAbby Sarkar
Howard Hughes Medical Institute and Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
Cell 147:487-9. 2011..In this issue, O'Brien et al. (2011) demonstrate that fly intestinal stem cells alter their division patterns in response to food availability to drive organ growth...
