Photo of Konrad Hochedlinger,  PhD

Konrad Hochedlinger, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 643-2075
Fax: (617) 643-3170


khochedlinger@helix.mgh.harvard.edu

Konrad Hochedlinger, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Professor, Stem Cell and Regenerative Biology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are interested in the biology of embryonic stem (ES) cells, which have the ability to give rise to all cell types of the body. The pluripotent state of ES cells is maintained by a set of transcription factors including Oct4, Sox2 and Nanog. Some of these factors appear to be important also in other cell types such as neural stem cells as well as in different biological processes such as nuclear reprogramming and cancer. Based on these observations, we have recently generated pluripotent cells directly from fibroblasts by ectopic expression of the trancription factors Oct4, Sox2, c-myc and Klf4. These cells are indistinguishable from ES cells and provide a platform for analyzing the molecular mechanism of epigenetic reprogramming as well as a system to generate patient-specific stem cells for studying and treating disease.

Publications

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  • Bar-Nur O, Verheul C, Sommer AG, Brumbaugh J, Schwarz BA, Lipchina I, Huebner AJ, Mostoslavsky G, Hochedlinger K. Lineage conversion induced by pluripotency factors involves transient passage through an iPSC stage. Nat Biotechnol 2015; 33:761-8. PubMed
  • Etchegaray JP, Chavez L, Huang Y, Ross KN, Choi J, Martinez-Pastor B, Walsh RM, Sommer CA, Lienhard M, Gladden A, Kugel S, Silberman DM, Ramaswamy S, Mostoslavsky G, Hochedlinger K, Goren A, Rao A, Mostoslavsky R. The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine. Nat Cell Biol 2015; 17:545-57. PubMed
  • Bar-Nur O, Brumbaugh J, Verheul C, Apostolou E, Pruteanu-Malinici I, Walsh RM, Ramaswamy S, Hochedlinger K. Small molecules facilitate rapid and synchronous iPSC generation. Nat Methods 2014. PubMed
  • Wu T, Liu Y, Wen D, Tseng Z, Tahmasian M, Zhong M, Rafii S, Stadtfeld M, Hochedlinger K, Xiao A. Histone variant H2A.X deposition pattern serves as a functional epigenetic mark for distinguishing the developmental potentials of iPSCs. Cell Stem Cell 2014; 15:281-94. PubMed
  • Vanner RJ, Remke M, Gallo M, Selvadurai HJ, Coutinho F, Lee L, Kushida M, Head R, Morrissy S, Zhu X, Aviv T, Voisin V, Clarke ID, Li Y, Mungall AJ, Moore RA, Ma Y, Jones SJ, Marra MA, Malkin D, Northcott PA, Kool M, Pfister SM, Bader G, Hochedlinger K, Korshunov A, Taylor MD, Dirks PB. Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma. Cancer Cell 2014; 26:33-47. PubMed
  • Foudi A, Kramer DJ, Qin J, Ye D, Behlich AS, Mordecai S, Preffer FI, Amzallag A, Ramaswamy S, Hochedlinger K, Orkin SH, Hock H. Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation. J Exp Med 2014. PubMed
  • Schwarz BA, Bar-Nur O, Silva JC, Hochedlinger K. Nanog is dispensable for the generation of induced pluripotent stem cells. Curr Biol 2014; 24:347-50. PubMed
  • Ferrari F, Apostolou E, Park PJ, Hochedlinger K. Rearranging the chromatin for pluripotency. Cell Cycle 2014; 13:167-8. PubMed
  • Das PP, Shao Z, Beyaz S, Apostolou E, Pinello L, De Los Angeles A, O'Brien K, Atsma JM, Fujiwara Y, Nguyen M, Ljuboja D, Guo G, Woo A, Yuan GC, Onder T, Daley G, Hochedlinger K, Kim J, Orkin SH. Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity. Mol Cell 2014; 53:32-48. PubMed
  • West JA, Cook A, Alver BH, Stadtfeld M, Deaton AM, Hochedlinger K, Park PJ, Tolstorukov MY, Kingston RE. Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming. Nat Commun 2014; 5:4719. PubMed
  • Wang L, Miao YL, Zheng X, Lackford B, Zhou B, Han L, Yao C, Ward JM, Burkholder A, Lipchina I, Fargo DC, Hochedlinger K, Shi Y, Williams CJ, Hu G. The THO complex regulates pluripotency gene mRNA export and controls embryonic stem cell self-renewal and somatic cell reprogramming. Cell Stem Cell 2013; 13:676-90. PubMed
  • Brumbaugh J, Hochedlinger K. Removing reprogramming roadblocks: Mbd3 depletion allows deterministic iPSC generation. Cell Stem Cell 2013; 13:379-81. PubMed
  • Walsh RM, Hochedlinger K. A variant CRISPR-Cas9 system adds versatility to genome engineering. Proc Natl Acad Sci U S A 2013; 110:15514-5. PubMed
  • Apostolou E, Ferrari F, Walsh RM, Bar-Nur O, Stadtfeld M, Cheloufi S, Stuart HT, Polo JM, Ohsumi TK, Borowsky ML, Kharchenko PV, Park PJ, Hochedlinger K. Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming. Cell Stem Cell 2013; 12:699-712. PubMed
  • Juuri E, Jussila M, Seidel K, Holmes S, Wu P, Richman J, Heikinheimo K, Chuong CM, Arnold K, Hochedlinger K, Klein O, Michon F, Thesleff I. Sox2 marks epithelial competence to generate teeth in mammals and reptiles. Development 2013; 140:1424-32. PubMed
  • Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M, Goldman SA. Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell 2013; 12:252-64. PubMed
  • Sarkar A, Hochedlinger K. The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell 2013; 12:15-30. PubMed
  • Hirata A, Utikal J, Yamashita S, Aoki H, Watanabe A, Yamamoto T, Okano H, Bardeesy N, Kunisada T, Ushijima T, Hara A, Jaenisch R, Hochedlinger K, Yamada Y. Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium. Development 2012; 140:66-75. PubMed
  • Hansson J, Rafiee MR, Reiland S, Polo JM, Gehring J, Okawa S, Huber W, Hochedlinger K, Krijgsveld J. Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency. Cell Rep 2012; 2:1579-92. PubMed
  • Polo JM, Anderssen E, Walsh RM, Schwarz BA, Nefzger CM, Lim SM, Borkent M, Apostolou E, Alaei S, Cloutier J, Bar-Nur O, Cheloufi S, Stadtfeld M, Figueroa ME, Robinton D, Natesan S, Melnick A, Zhu J, Ramaswamy S, Hochedlinger K. A molecular roadmap of reprogramming somatic cells into iPS cells. Cell 2012; 151:1617-32. PubMed
  • Cheloufi S, Hochedlinger K. Reproductive biology: Stem cells bear eggs. Nature 2012; 491:535-6. PubMed
  • Buckley SM, Aranda-Orgilles B, Strikoudis A, Apostolou E, Loizou E, Moran-Crusio K, Farnsworth CL, Koller AA, Dasgupta R, Silva JC, Stadtfeld M, Hochedlinger K, Chen EI, Aifantis I. Regulation of Pluripotency and Cellular Reprogramming by the Ubiquitin-Proteasome System. Cell Stem Cell 2012. PubMed
  • Qin J, Whyte WA, Anderssen E, Apostolou E, Chen HH, Akbarian S, Bronson RT, Hochedlinger K, Ramaswamy S, Young RA, Hock H. The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development. Cell Stem Cell 2012; 11:319-32. PubMed
  • Juuri E, Saito K, Ahtiainen L, Seidel K, Tummers M, Hochedlinger K, Klein OD, Thesleff I, Michon F. Sox2+ stem cells contribute to all epithelial lineages of the tooth via Sfrp5+ progenitors. Dev Cell 2012; 23:317-28. PubMed
  • Blanpain C, Daley GQ, Hochedlinger K, Passegué E, Rossant J, Yamanaka S. Stem cells assessed. Nat Rev Mol Cell Biol 2012; 13:471-6. PubMed
  • Hochedlinger K. From MYOD1 to iPS cells. Nat Rev Mol Cell Biol 2010; 11:817. PubMed
  • Walsh RM, Hochedlinger K. Modeling Rett syndrome with stem cells. Cell 2010; 143:499-500. PubMed
  • Serwold T, Hochedlinger K, Swindle J, Hedgpeth J, Jaenisch R, Weissman IL. T-cell receptor-driven lymphomagenesis in mice derived from a reprogrammed T cell. Proc Natl Acad Sci U S A 2010; 107:18939-43. PubMed
  • Stadtfeld M, Hochedlinger K. Induced pluripotency: history, mechanisms, and applications. Genes Dev 2010; 24:2239-63. PubMed
  • Brady BL, Oropallo MA, Yang-Iott KS, Serwold T, Hochedlinger K, Jaenisch R, Weissman IL, Bassing CH. Position-dependent silencing of germline Vbeta segments on TCRbeta alleles containing preassembled VbetaDJbetaCbeta1 genes. J Immunol 2010; 185:3564-73. PubMed
  • Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apostolou E, Stadtfeld M, Li Y, Shioda T, Natesan S, Wagers AJ, Melnick A, Evans T, Hochedlinger K. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 2010; 28:848-55. PubMed
  • Polo JM, Hochedlinger K. When fibroblasts MET iPSCs. Cell Stem Cell 2010; 7:5-6. PubMed
  • Buecker C, Chen HH, Polo JM, Daheron L, Bu L, Barakat TS, Okwieka P, Porter A, Gribnau J, Hochedlinger K, Geijsen N. A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells. Cell Stem Cell 2010; 6:535-46. PubMed
  • Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K. Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 2010; 465:175-81. PubMed
  • Hochedlinger K. Your inner healers. Sci Am 2010; 302:46-53. PubMed
  • Yang-Iott KS, Carpenter AC, Rowh MA, Steinel N, Brady BL, Hochedlinger K, Jaenisch R, Bassing CH. TCR beta feedback signals inhibit the coupling of recombinationally accessible V beta 14 segments with DJ beta complexes. J Immunol 2010; 184:1369-78. PubMed
  • Stadtfeld M, Maherali N, Borkent M, Hochedlinger K. A reprogrammable mouse strain from gene-targeted embryonic stem cells. Nat Methods 2009; 7:53-5. PubMed
  • Belmonte JC, Ellis J, Hochedlinger K, Yamanaka S. Induced pluripotent stem cells and reprogramming: seeing the science through the hype. Nat Rev Genet 2009; 10:878-83. PubMed
  • Maherali N, Hochedlinger K. Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMyc. Curr Biol 2009; 19:1718-23. PubMed
  • Utikal J, Maherali N, Kulalert W, Hochedlinger K. Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci 2009; 122:3502-10. PubMed
  • Chen L, Yabuuchi A, Eminli S, Takeuchi A, Lu CW, Hochedlinger K, Daley GQ. Cross-regulation of the Nanog and Cdx2 promoters. Cell Res 2009; 19:1052-61. PubMed
  • Eminli S, Foudi A, Stadtfeld M, Maherali N, Ahfeldt T, Mostoslavsky G, Hock H, Hochedlinger K. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 2009; 41:968-76. PubMed
  • Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, Khalil A, Rheinwald JG, Hochedlinger K. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 2009; 460:1145-8. PubMed
  • Geijsen N, Hochedlinger K. gPS navigates germ cells to pluripotency. Cell Stem Cell 2009; 5:3-4. PubMed
  • Stadtfeld M,Hochedlinger K. Without a trace? PiggyBac-ing toward pluripotency. Nat Methods 2009; 6:329-30. PubMed
  • Deng J,Shoemaker R,Xie B,Gore A,LeProust EM,Antosiewicz-Bourget J,Egli D,Maherali N,Park IH,Yu J,Daley GQ,Eggan K,Hochedlinger K,Thomson J,Wang W,Gao Y,Zhang K. Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat Biotechnol 2009; 27:353-60. PubMed
  • Sommer CA,Stadtfeld M,Murphy GJ,Hochedlinger K,Kotton DN,Mostoslavsky G. Induced pluripotent stem cell generation using a single lentiviral stem cell cassette. Stem Cells 2008; 27:543-9. PubMed
  • Hochedlinger K,Plath K. Epigenetic reprogramming and induced pluripotency. Development 2009; 136:509-23. PubMed
  • Varas F,Stadtfeld M,de Andres-Aguayo L,Maherali N,di Tullio A,Pantano L,Notredame C,Hochedlinger K,Graf T. Fibroblast-derived induced pluripotent stem cells show no common retroviral vector insertions. Stem Cells 2008; 27:300-6. PubMed
  • Foudi A,Hochedlinger K,Van Buren D,Schindler JW,Jaenisch R,Carey V,Hock H. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol 2008; 27:84-90. PubMed
  • Maherali N,Hochedlinger K. Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell 2008; 3:595-605. PubMed
  • Stadtfeld M,Nagaya M,Utikal J,Weir G,Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science 2008; 322:945-9. PubMed
  • Eminli S,Utikal J,Arnold K,Jaenisch R,Hochedlinger K. Reprogramming of neural progenitor cells into induced pluripotent stem cells in the absence of exogenous Sox2 expression. Stem Cells 2008; 26:2467-74. PubMed
  • Maherali N,Ahfeldt T,Rigamonti A,Utikal J,Cowan C,Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 2008; 3:340-5. PubMed
  • Park IH,Arora N,Huo H,Maherali N,Ahfeldt T,Shimamura A,Lensch MW,Cowan C,Hochedlinger K,Daley GQ. Disease-specific induced pluripotent stem cells. Cell 2008; 134:877-86. PubMed
  • Stadtfeld M,Brennand K,Hochedlinger K. Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Curr Biol 2008; 18:890-4. PubMed
  • Stadtfeld M, Maherali N, Breault DT, Hochedlinger K. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2008; 2:230-40. PubMed
  • Lengner CJ, Camargo FD, Hochedlinger K, Welstead GG, Zaidi S, Gokhale S, Scholer HR, Tomilin A, Jaenisch R. Oct4 expression is not required for mouse somatic stem cell self-renewal. Cell Stem Cell 2007; 1:403-15. PubMed
  • Hyun I, Hochedlinger K, Jaenisch R, Yamanaka S. New advances in iPS cell research do not obviate the need for human embryonic stem cells. Cell Stem Cell 2008; 1:367-8. PubMed
  • Hochedlinger K. Konrad Hochedlinger: the new kid of nuclear reprogramming. J Cell Biol 2007; 178:1098-9. PubMed
  • Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 2007; 448:318-24. PubMed
  • Serwold T, Hochedlinger K, Inlay MA, Jaenisch R, Weissman IL. Early TCR expression and aberrant T cell development in mice with endogenous prerearranged T cell receptor genes. J Immunol 2007; 179:928-38. PubMed
  • Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 2008; 1:55-70. PubMed
  • Hochedlinger K, Jaenisch R. On the cloning of animals from terminally differentiated cells. Nat Genet 2007; 39:136-7; author reply 137-8. PubMed
  • Hochedlinger K, Jaenisch R. Nuclear reprogramming and pluripotency. Nature 2006; 441:1061-7. PubMed
  • Brambrink T, Hochedlinger K, Bell G, Jaenisch R. ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable. Proc Natl Acad Sci U S A 2006; 103:933-8. PubMed
  • Beard C, Hochedlinger K, Plath K, Wutz A, Jaenisch R. Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells. Genesis 2006; 44:23-8. PubMed
  • Hochedlinger K, Yamada Y, Beard C, Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 2005; 121:465-77. PubMed
  • Koralov SB, Novobrantseva TI, Hochedlinger K, Jaenisch R, Rajewsky K. Direct in vivo VH to JH rearrangement violating the 12/23 rule. J Exp Med 2005; 201:341-8. PubMed
  • Gribnau J, Luikenhuis S, Hochedlinger K, Monkhorst K, Jaenisch R. X chromosome choice occurs independently of asynchronous replication timing. J Cell Biol 2005; 168:365-73. PubMed
  • Blelloch RH, Hochedlinger K, Yamada Y, Brennan C, Kim M, Mintz B, Chin L, Jaenisch R. Nuclear cloning of embryonal carcinoma cells. Proc Natl Acad Sci U S A 2004; 101:13985-90. PubMed
  • Sabapathy K, Hochedlinger K, Nam SY, Bauer A, Karin M, Wagner EF. Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation. Mol Cell 2004; 15:713-25. PubMed
  • Hochedlinger K, Blelloch R, Brennan C, Yamada Y, Kim M, Chin L, Jaenisch R. Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev 2004; 18:1875-85. PubMed
  • Hochedlinger K, Jaenisch R. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med 2003; 349:275-86. PubMed
  • Gribnau J, Hochedlinger K, Hata K, Li E, Jaenisch R. Asynchronous replication timing of imprinted loci is independent of DNA methylation, but consistent with differential subnuclear localization. Genes Dev 2003; 17:759-73. PubMed
  • Hochedlinger K, Jaenisch R. Nuclear transplantation: lessons from frogs and mice. Curr Opin Cell Biol 2002; 14:741-8. PubMed
  • Humpherys D, Eggan K, Akutsu H, Friedman A, Hochedlinger K, Yanagimachi R, Lander ES, Golub TR, Jaenisch R. Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei. Proc Natl Acad Sci U S A 2002; 99:12889-94. PubMed
  • Rideout WM, Hochedlinger K, Kyba M, Daley GQ, Jaenisch R. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell 2002; 109:17-27. PubMed
  • Hochedlinger K, Wagner EF, Sabapathy K. Differential effects of JNK1 and JNK2 on signal specific induction of apoptosis. Oncogene 2002; 21:2441-5. PubMed
  • Hochedlinger K, Jaenisch R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 2002; 415:1035-8. PubMed
  • Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout WM, Biniszkiewicz D, Yanagimachi R, Jaenisch R. Epigenetic instability in ES cells and cloned mice. Science 2001; 293:95-7. PubMed
  • Eggan K, Akutsu H, Hochedlinger K, Rideout W, Yanagimachi R, Jaenisch R. X-Chromosome inactivation in cloned mouse embryos. Science 2000; 290:1578-81. PubMed
  • Sabapathy K, Jochum W, Hochedlinger K, Chang L, Karin M, Wagner EF. Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mech Dev 1999; 89:115-24. PubMed
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