Rudolf Jaenisch

Summary

Affiliation: Massachusetts Institute of Technology
Country: USA

Publications

  1. doi request reprint Nuclear cloning and direct reprogramming: the long and the short path to Stockholm
    Rudolf Jaenisch
    Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell Stem Cell 11:744-7. 2012
  2. pmc Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation
    G Csankovszki
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    J Cell Biol 153:773-84. 2001
  3. ncbi request reprint DNA methylation and imprinting: why bother?
    R Jaenisch
    Whitehead Institute, Massachusetts Institute of Technology, Cambridge 02142, USA
    Trends Genet 13:323-9. 1997
  4. doi request reprint Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming
    Rudolf Jaenisch
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 132:567-82. 2008
  5. pmc X chromosome choice occurs independently of asynchronous replication timing
    Joost Gribnau
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 168:365-73. 2005
  6. pmc Transgenic mice with defined combinations of drug-inducible reprogramming factors
    Styliani Markoulaki
    The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Biotechnol 27:169-71. 2009
  7. pmc H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment
    Menno P Creyghton
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 135:649-61. 2008
  8. pmc Dissecting direct reprogramming through integrative genomic analysis
    Tarjei S Mikkelsen
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 454:49-55. 2008
  9. pmc Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors
    Jongpil Kim
    Whitehead Institute for Biomedical Research and, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Stem Cells 29:992-1000. 2011
  10. ncbi request reprint In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state
    Marius Wernig
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nature 448:318-24. 2007

Research Grants

  1. Programming and Reprogramming Human Cells
    Rudolf Jaenisch; Fiscal Year: 2010
  2. GENOMIC IMPRINTING AND THE CLONING OF MICE
    Rudolf Jaenisch; Fiscal Year: 2007
  3. Nuclear Cloning and the Reprogramming of the Genome
    Rudolf Jaenisch; Fiscal Year: 2007
  4. Epigenetics, Stem Cells, and Cancer
    Rudolf Jaenisch; Fiscal Year: 2010
  5. Epigenetics, Stem Cells, and Cancer
    Rudolf Jaenisch; Fiscal Year: 2007
  6. DNA METHYLATION, GENE REGULATION, AND CANCER
    Rudolf Jaenisch; Fiscal Year: 2005

Collaborators

Detail Information

Publications170 found, 100 shown here

  1. doi request reprint Nuclear cloning and direct reprogramming: the long and the short path to Stockholm
    Rudolf Jaenisch
    Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell Stem Cell 11:744-7. 2012
    ..The two winners of the 2012 Nobel Prize in Physiology or Medicine share more than just this honor; they are both also fearless adventurers, in science and beyond...
  2. pmc Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation
    G Csankovszki
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    J Cell Biol 153:773-84. 2001
    ....
  3. ncbi request reprint DNA methylation and imprinting: why bother?
    R Jaenisch
    Whitehead Institute, Massachusetts Institute of Technology, Cambridge 02142, USA
    Trends Genet 13:323-9. 1997
    ..However, our understanding of molecular details of the imprinting process, as well as evolutionary considerations, is rather consistent with imprinting having no intrinsic role in mammalian development...
  4. doi request reprint Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming
    Rudolf Jaenisch
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 132:567-82. 2008
    ....
  5. pmc X chromosome choice occurs independently of asynchronous replication timing
    Joost Gribnau
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 168:365-73. 2005
    ....
  6. pmc Transgenic mice with defined combinations of drug-inducible reprogramming factors
    Styliani Markoulaki
    The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Biotechnol 27:169-71. 2009
    ..This approach creates a defined system for studying reprogramming mechanisms and allows screening of genetically homogeneous cells for compounds that can replace any transcription factor required for iPS cell derivation...
  7. pmc H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment
    Menno P Creyghton
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 135:649-61. 2008
    ..Thus, H2AZ, together with PcG proteins, may establish specialized chromatin states in ES cells necessary for the proper execution of developmental gene expression programs...
  8. pmc Dissecting direct reprogramming through integrative genomic analysis
    Tarjei S Mikkelsen
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 454:49-55. 2008
    ..We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process...
  9. pmc Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors
    Jongpil Kim
    Whitehead Institute for Biomedical Research and, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Stem Cells 29:992-1000. 2011
    ....
  10. ncbi request reprint In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state
    Marius 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...
  11. pmc Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing
    Heinz G Linhart
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Genes Dev 21:3110-22. 2007
    ....
  12. pmc Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression
    Qing Gao
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 108:18061-6. 2011
    ..Our results suggest that Dnmt3a may act like a tumor-suppressor gene in lung tumor progression and may be a critical determinant of lung cancer malignancy...
  13. pmc Mir-290-295 deficiency in mice results in partially penetrant embryonic lethality and germ cell defects
    Lea A Medeiros
    Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 108:14163-8. 2011
    ..Female mir-290-295(-/-) mice are unable to recover and are sterile, due to premature ovarian failure...
  14. pmc Suppression of intestinal neoplasia by deletion of Dnmt3b
    Haijiang Lin
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02141, USA
    Mol Cell Biol 26:2976-83. 2006
    ....
  15. pmc Control of developmental regulators by Polycomb in human embryonic stem cells
    Tong Ihn Lee
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 125:301-13. 2006
    ..These results indicate that PRC2 occupies a special set of developmental genes in ES cells that must be repressed to maintain pluripotency and that are poised for activation during ES cell differentiation...
  16. pmc Genome-scale DNA methylation maps of pluripotent and differentiated cells
    Alexander Meissner
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 454:766-70. 2008
    ..More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine...
  17. pmc ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable
    Tobias 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...
  18. pmc Direct reprogramming of fibroblasts into embryonic Sertoli-like cells by defined factors
    Yosef Buganim
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell Stem Cell 11:373-86. 2012
    ....
  19. pmc Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells
    Tobias Brambrink
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell Stem Cell 2:151-9. 2008
    ..Importantly, the virally transduced cDNAs needed to be expressed for at least 12 days in order to generate iPS cells. Our results are a step toward understanding some of the molecular events governing epigenetic reprogramming...
  20. ncbi request reprint Nuclear transplantation, embryonic stem cells and the potential for cell therapy
    Konrad 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...
  21. pmc A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types
    Marius Wernig
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Biotechnol 26:916-24. 2008
    ..This system facilitates the characterization of reprogramming and provides a tool for genetic or chemical screens to enhance reprogramming...
  22. pmc Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus
    Robert Blelloch
    Whitehead Instituteand Department of Biology, Massachusetts Institute of Technology, Cambridge, USA
    Stem Cells 24:2007-13. 2006
    ..Our results provide functional evidence that the differentiation and epigenetic state of the donor nucleus influences reprogramming efficiency...
  23. pmc Single-gene transgenic mouse strains for reprogramming adult somatic cells
    Bryce W Carey
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Methods 7:56-9. 2010
    ..Because reprogramming factors are carried on a single polycistronic construct, the mice can be easily maintained, and the transgene can be easily transferred into other genetic backgrounds...
  24. ncbi request reprint Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin
    Jacob Hanna
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 318:1920-3. 2007
    ..The problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells can be considered for human therapy...
  25. doi request reprint Tet1 is critical for neuronal activity-regulated gene expression and memory extinction
    Andrii Rudenko
    The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Howard Hughes Medical Institute, Cambridge, MA 02142, USA
    Neuron 79:1109-22. 2013
    ..In summary, we show that neuronal Tet1 regulates normal DNA methylation levels, expression of activity-regulated genes, synaptic plasticity, and memory extinction...
  26. pmc Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development
    Meelad M Dawlaty
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Dev Cell 24:310-23. 2013
    ..Our data show that loss of both enzymes is compatible with development but promotes hypermethylation and compromises imprinting. The data also suggest a significant contribution of Tet3 to hydroxylation of 5mC during development...
  27. pmc Nuclear cloning of embryonal carcinoma cells
    Robert 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...
  28. ncbi request reprint Polycomb complexes repress developmental regulators in murine embryonic stem cells
    Laurie A Boyer
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 441:349-53. 2006
    ..Our results indicate that dynamic repression of developmental pathways by Polycomb complexes may be required for maintaining ES cell pluripotency and plasticity during embryonic development...
  29. ncbi request reprint Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei
    Alex Bortvin
    Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
    Development 130:1673-80. 2003
    ..These observations suggest that failure to reactivate the full spectrum of these Oct4-related genes may contribute to embryonic lethality in somatic-cell clones...
  30. ncbi request reprint Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells
    Caroline 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...
  31. ncbi request reprint YAP1 increases organ size and expands undifferentiated progenitor cells
    Fernando D Camargo
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Curr Biol 17:2054-60. 2007
    ..Our data show that the Hippo signaling pathway regulates organ size in mammals and can act on stem cell compartments, indicating a potential link between stem/progenitor cells, organ size, and cancer...
  32. pmc Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2
    Emanuela Giacometti
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 104:1931-6. 2007
    ..Our results indicate that postnatal, neuron-specific activation of MeCP2 as late as 2-4 weeks of age significantly prolonged the lifespan of mutant animals and delayed the onset of neurologic symptoms...
  33. pmc A chromatin landmark and transcription initiation at most promoters in human cells
    Matthew G Guenther
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 130:77-88. 2007
    ..These observations extend to differentiated cells, suggesting that transcription initiation at most genes is a general phenomenon in human cells...
  34. pmc Oct4 expression is not required for mouse somatic stem cell self-renewal
    Christopher 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...
  35. pmc Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice
    Daniela Tropea
    Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 106:2029-34. 2009
    ..Our results thus strongly suggest IGF-1 as a candidate for pharmacological treatment of RTT and potentially of other CNS disorders caused by delayed synapse maturation...
  36. pmc Reprogramming of a melanoma genome by nuclear transplantation
    Konrad 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...
  37. pmc Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase
    Yosef Buganim
    The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 150:1209-22. 2012
    ..Finally, downstream factors derived from the late phase, which do not include Oct4, Sox2, Klf4, c-Myc, and Nanog, can activate the pluripotency circuitry...
  38. pmc Functional integration of dopaminergic neurons directly converted from mouse fibroblasts
    Jongpil Kim
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Cell Stem Cell 9:413-9. 2011
    ..Thus, iDA neurons generated from abundant somatic fibroblasts by direct lineage reprogramming hold promise for modeling neurodegenerative disease and for cell-based therapies of PD...
  39. pmc Analysis of the mouse embryonic stem cell regulatory networks obtained by ChIP-chip and ChIP-PET
    Divya Mathur
    Department of Biology, Massachusetts Institute of Technology, Ames Street, Cambridge, MA 02139, USA
    Genome Biol 9:R126. 2008
    ..Recent evidence with comparing multiple technologies suggests that expanding these datasets using different platforms would be a useful resource for examining the mechanisms underlying pluripotency regulation...
  40. pmc Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
    Tarjei S Mikkelsen
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
    Nature 448:553-60. 2007
    ..This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations...
  41. pmc Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency
    Jacob Hanna
    The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 133:250-64. 2008
    ..Our study provides definite proof for the direct nuclear reprogramming of terminally differentiated adult cells to pluripotency...
  42. pmc Metastable pluripotent states in NOD-mouse-derived ESCs
    Jacob Hanna
    The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell Stem Cell 4:513-24. 2009
    ..Our findings suggest that stem cells from different genetic backgrounds can assume distinct states of pluripotency in vitro, the stability of which is regulated by endogenous genetic determinants and can be modified by exogenous factors...
  43. pmc Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors
    Frank Soldner
    The Whitehead Institute, Cambridge Center, MA 02142, USA
    Cell 136:964-77. 2009
    ..Our results indicate that residual transgene expression in virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease...
  44. doi request reprint Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases
    Dirk Hockemeyer
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Biotechnol 27:851-7. 2009
    ..Finally, we targeted the PITX3 gene, demonstrating that ZFNs can be used to generate reporter cells by targeting non-expressed genes in hESCs and hiPSCs...
  45. ncbi request reprint Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues
    Konrad 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...
  46. ncbi request reprint Induction of tumors in mice by genomic hypomethylation
    François Gaudet
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Science 300:489-92. 2003
    ..These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability...
  47. pmc Direct cell reprogramming is a stochastic process amenable to acceleration
    Jacob Hanna
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Nature 462:595-601. 2009
    ....
  48. pmc A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells
    Grace X Y Zheng
    MIT Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts, USA
    PLoS Genet 7:e1002054. 2011
    ..Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target...
  49. ncbi request reprint The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression
    Qiang Chang
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Neuron 49:341-8. 2006
    ..Our results provide in vivo evidence for a functional interaction between Mecp2 and Bdnf and demonstrate the physiological significance of altered BDNF expression/signaling in RTT disease progression...
  50. doi request reprint Reprogramming factor stoichiometry influences the epigenetic state and biological properties of induced pluripotent stem cells
    Bryce W Carey
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Cell Stem Cell 9:588-98. 2011
    ..This concept complicates efforts to define a "generic" epigenetic state of iPSCs and ESCs and should be considered when comparing different iPS and ES cell lines...
  51. pmc Surface-engineered substrates for improved human pluripotent stem cell culture under fully defined conditions
    Krishanu Saha
    The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 108:18714-9. 2011
    ....
  52. ncbi request reprint Micromanipulating dosage compensation: understanding X-chromosome inactivation through nuclear transplantation
    Kevin Eggan
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    Semin Cell Dev Biol 14:349-58. 2003
    ..These results suggest epigenetic information established during embryonic X-inactivation is functionally equivalent to the gametic imprint...
  53. pmc Histone H3K27ac separates active from poised enhancers and predicts developmental state
    Menno P Creyghton
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:21931-6. 2010
    ..Furthermore, poised enhancer networks provide clues to unrealized developmental programs. Finally, we show that enhancers are reset during nuclear reprogramming...
  54. pmc Reprogramming of murine and human somatic cells using a single polycistronic vector
    Bryce W Carey
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 106:157-62. 2009
    ..In addition we have generated human induced pluripotent stem (hiPS) cell lines from human keratinocytes, demonstrating that a single polycistronic virus can reprogram human somatic cells...
  55. pmc Opposing effects of DNA hypomethylation on intestinal and liver carcinogenesis
    Yasuhiro Yamada
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 102:13580-5. 2005
    ..These findings support the notion of a dual role for DNA hypomethylation in suppressing later stages of intestinal tumorigenesis, but promoting early lesions in the colon and liver through an LOH mechanism...
  56. pmc Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs
    Jacob Hanna
    The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:9222-7. 2010
    ..The generation of validated "naïve" human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research...
  57. pmc TALEN-mediated editing of the mouse Y chromosome
    Haoyi Wang
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Biotechnol 31:530-2. 2013
    ..TALEN-mediated gene editing is a useful tool for dissecting the biology of the Y chromosome...
  58. pmc Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease
    Marius Wernig
    The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:5856-61. 2008
    ..Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model...
  59. pmc Genes methylated by DNA methyltransferase 3b are similar in mouse intestine and human colon cancer
    Eveline J Steine
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts, USA
    J Clin Invest 121:1748-52. 2011
    ..This supports the concept that transient stressors can cause permanent epigenetic changes in somatic stem cells and that these accumulate over the lifetime of an organism in analogy to DNA mutations...
  60. pmc Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis
    Alexander Meissner
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Nucleic Acids Res 33:5868-77. 2005
    ..Near-complete bisulfite conversion and largely unbiased representation of RRBS libraries suggest that random shotgun bisulfite sequencing can be scaled to a genome-wide approach...
  61. pmc Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei
    David Humpherys
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 99:12889-94. 2002
    ..Our results demonstrate frequent abnormal gene expression in clones, in which most expression abnormalities appear common to the NT procedure whereas others appear to reflect the particular donor nucleus...
  62. pmc Folate deficiency induces genomic uracil misincorporation and hypomethylation but does not increase DNA point mutations
    Heinz G Linhart
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Gastroenterology 136:227-235.e3. 2009
    ..Our aim was to analyze the genetic and epigenetic consequences of folate deficiency and to investigate whether impairment of the uracil base excision repair pathway can enhance its effects...
  63. pmc Sprouty-2 regulates oncogenic K-ras in lung development and tumorigenesis
    Alice T Shaw
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston 02114, USA
    Genes Dev 21:694-707. 2007
    ..These findings indicate that in the lung, Sprouty-2 plays a critical role in the regulation of oncogenic K-ras, and implicate counter-regulatory mechanisms in the pathogenesis of Ras-based disease...
  64. pmc Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells
    Matthew G Guenther
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell Stem Cell 7:249-57. 2010
    ..Although some variation in chromatin structure and gene expression was observed in these cell lines, these variations did not serve to distinguish ESCs from iPSCs...
  65. pmc Asynchronous replication timing of imprinted loci is independent of DNA methylation, but consistent with differential subnuclear localization
    Joost Gribnau
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Genes Dev 17:759-73. 2003
    ....
  66. ncbi request reprint Global loss of imprinting leads to widespread tumorigenesis in adult mice
    Teresa M Holm
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, Boston, USA
    Cancer Cell 8:275-85. 2005
    ..These data demonstrate that LOI alone can predispose cells to tumorigenesis and identify a pathway through which immortality conferred by LOI lowers the threshold for transformation...
  67. ncbi request reprint Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells
    Alexander Meissner
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge Massachusetts 02142, USA
    Nat Biotechnol 25:1177-81. 2007
    ..Here we demonstrate that reprogrammed pluripotent cells can be isolated from genetically unmodified somatic donor cells solely based upon morphological criteria...
  68. pmc Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells
    Alexander Marson
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 134:521-33. 2008
    ..These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity...
  69. pmc Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development
    Meelad M Dawlaty
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell Stem Cell 9:166-75. 2011
    ..Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development...
  70. ncbi request reprint Mice cloned from olfactory sensory neurons
    Kevin Eggan
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 428:44-9. 2004
    ....
  71. ncbi request reprint Differentiation of F1 embryonic stem cells into viable male and female mice by tetraploid embryo complementation
    Kevin Eggan
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Methods Enzymol 365:25-39. 2003
  72. doi request reprint Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations
    Christopher J Lengner
    Whitehead Institute for Biomedical Sciences, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 141:872-83. 2010
    ..These findings indicate that the human blastocyst contains pre-X-inactivation cells and that this state is preserved in vitro through culture under physiological oxygen...
  73. ncbi request reprint Ablation of de novo DNA methyltransferase Dnmt3a in the nervous system leads to neuromuscular defects and shortened lifespan
    Suzanne Nguyen
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Dev Dyn 236:1663-76. 2007
    ..Our results implicate a role for Dnmt3a in the neuromuscular control of motor movement...
  74. pmc Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters
    Andrea Ventura
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 132:875-86. 2008
    ..These results provide key insights into the physiologic functions of this family of microRNAs and suggest a link between the oncogenic properties of miR-17 approximately 92 and its functions during B lymphopoiesis and lung development...
  75. ncbi request reprint Role of the Xist gene in X chromosome choosing
    Y Marahrens
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Cell 92:657-64. 1998
    ..In conflict with the prevailing view of how choosing occurs, the element identified by the deletion plays a positive role in the choice mechanism and forces a reassessment of how X chromosome choosing is thought to occur...
  76. ncbi request reprint A 450 kb transgene displays properties of the mammalian X-inactivation center
    J T Lee
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA
    Cell 86:83-94. 1996
    ..These results argue that the Xic is contained within 450 kb and that these sequences are sufficient for chromosome counting, choosing, and initiation of X inactivation...
  77. ncbi request reprint Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not of nonimprinted genes
    K L Tucker
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Genes Dev 10:1008-20. 1996
    ....
  78. pmc Core transcriptional regulatory circuitry in human embryonic stem cells
    Laurie A Boyer
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Cell 122:947-56. 2005
    ..These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal...
  79. ncbi request reprint Chromosomal silencing and localization are mediated by different domains of Xist RNA
    Anton Wutz
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Genet 30:167-74. 2002
    ..Association of Xist RNA with chromatin is mediated by functionally redundant sequences that act cooperatively and are dispersed throughout the remainder of Xist but show little or no homology...
  80. ncbi request reprint Myogenin can substitute for Myf5 in promoting myogenesis but less efficiently
    Y Wang
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA
    Development 124:2507-13. 1997
    ....
  81. pmc Antisense transcription through the Xist locus mediates Tsix function in embryonic stem cells
    S Luikenhuis
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Mol Cell Biol 21:8512-20. 2001
    ..These results for the first time establish a function for antisense transcription in the regulation of X inactivation...
  82. ncbi request reprint Xist-deficient mice are defective in dosage compensation but not spermatogenesis
    Y Marahrens
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Genes Dev 11:156-66. 1997
    ..Our results indicate that the Xist RNA is required for female dosage compensation but plays no role in spermatogenesis...
  83. ncbi request reprint Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice
    R Z Chen
    The Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Genet 27:327-31. 2001
    ..Mecp2 deficiency in these neurons is sufficient to cause neuronal dysfunction with symptomatic manifestation similar to Rett syndrome...
  84. pmc Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain
    Matthew Tudor
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, MA 02142, USA
    Proc Natl Acad Sci U S A 99:15536-41. 2002
    ..This result suggests that Mecp2 deficiency leads to subtle gene expression changes in mutant brains which may be associated with the phenotypic changes observed...
  85. pmc Transnuclear mice with predefined T cell receptor specificities against Toxoplasma gondii obtained via SCNT
    Oktay Kirak
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 328:243-8. 2010
    ..The relative ease and speed with which such transnuclear models can be obtained holds promise for the construction of other disease models...
  86. ncbi request reprint The pluripotency regulator Oct4: a role in somatic stem cells?
    Christopher J Lengner
    The Whitehead Institute for Biomedical Research, Cambridge, Massachussets 01242, USA
    Cell Cycle 7:725-8. 2008
    ..Here we contrast pathways known to govern pluripotency in embryonic stem cells with those in adult stem cells and critically discuss the concept of pluripotency in adult stem cells of the mammalian soma...
  87. ncbi request reprint Molecular control of pluripotency
    Laurie A Boyer
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Curr Opin Genet Dev 16:455-62. 2006
    ..These studies provide a conceptual framework for understanding pluripotency and lineage-specification at the molecular level...
  88. pmc Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues
    Jacob H Hanna
    The Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Cell 143:508-25. 2010
    ..Here we review recent advances in this rapidly moving field and emphasize unresolved and controversial questions...
  89. pmc Developmentally regulated alterations in Polycomb repressive complex 1 proteins on the inactive X chromosome
    Kathrin Plath
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    J Cell Biol 167:1025-35. 2004
    ..Our results implicate mPRC1 in X inactivation and suggest that the regulated assembly of PcG protein complexes on the Xi contributes to this multistep process...
  90. ncbi request reprint Nuclear transplantation: lessons from frogs and mice
    Konrad Hochedlinger
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Curr Opin Cell Biol 14:741-8. 2002
    ..Indeed, gene expression analyses and extensive phenotypic characterisation of cloned animals suggest that most, if not all, clones suffer from at least subtle abnormalities...
  91. ncbi request reprint Clonal cell lines produced by infection of neocortical neuroblasts using multiple oncogenes transduced by retroviruses
    J Chun
    Whitehead Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
    Mol Cell Neurosci 7:304-21. 1996
    ..These cell lines may represent developing neocortical neuroblasts blocked from complete differentiation, and they should be useful in the isolation and analysis of genes involved in early neocortical development...
  92. ncbi request reprint DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals
    G Fan
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    J Neurosci 21:788-97. 2001
    ..However, these mutant cells were eliminated quickly from the brain within 3 weeks of postnatal life. Thus, hypomethylated CNS neurons were impaired functionally and were selected against at postnatal stages...
  93. ncbi request reprint Serrate2 is disrupted in the mouse limb-development mutant syndactylism
    A Sidow
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Nature 389:722-5. 1997
    ..In addition to cloning the sm gene, we have mapped three modifiers of sm, for which we suggest possible candidate genes...
  94. ncbi request reprint Long-range cis effects of ectopic X-inactivation centres on a mouse autosome
    J T Lee
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Nature 386:275-9. 1997
    ..Thus, the potential for chromosome-wide gene regulation is not intrinsic to X-chromosome DNA, but can also occur on autosomes possessing the Xic...
  95. ncbi request reprint Germ line transmission of a yeast artificial chromosome spanning the murine alpha 1(I) collagen locus
    W M Strauss
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142
    Science 259:1904-7. 1993
    ..Both assays indicated that the transgene was expressed at levels comparable to the endogenous collagen gene...
  96. ncbi request reprint Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation
    L Jackson-Grusby
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Genet 27:31-9. 2001
    ....
  97. ncbi request reprint X chromosome inactivation is mediated by Xist RNA stabilization
    B Panning
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Cell 90:907-16. 1997
    ....
  98. pmc Ubiquitous expression and embryonic requirement for RNA polymerase II coactivator subunit Srb7 in mice
    M Tudor
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142 USA
    Genes Dev 13:2365-8. 1999
    ....
  99. ncbi request reprint Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development
    M A Rudnicki
    Whitehead Institute, Massachusetts Institute of Technology, Cambridge 02142
    Cell 71:383-90. 1992
    ..Our results indicate that MyoD is dispensable for skeletal muscle development in mice, revealing some degree of functional redundancy in the control of the skeletal myogenic developmental program...
  100. pmc Messenger RNAs encoding mouse histone macroH2A1 isoforms are expressed at similar levels in male and female cells and result from alternative splicing
    T P Rasmussen
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Nucleic Acids Res 27:3685-9. 1999
    ..1 at low levels if at all. The relatively abundant expression of mH2A1 in both sexes suggests that mH2A1 has functions in addition to a possible involvement in X chromosome inactivation...
  101. ncbi request reprint A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation
    A Wutz
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Mol Cell 5:695-705. 2000
    ..Xist had to be activated within 48 hr of differentiation to effect silencing, suggesting that reversible repression by Xist is a required initiation step that might occur during normal X inactivation in female cells...

Research Grants20

  1. Programming and Reprogramming Human Cells
    Rudolf Jaenisch; Fiscal Year: 2010
    ..Once the experimental obstacles have been overcome, it is our long-term goal to use patient-specific iPS cell lines to study the basis of complex human diseases. ..
  2. GENOMIC IMPRINTING AND THE CLONING OF MICE
    Rudolf Jaenisch; Fiscal Year: 2007
    ..This program attempts to define the biological parameters which limit the nuclear cloning approach. ..
  3. Nuclear Cloning and the Reprogramming of the Genome
    Rudolf Jaenisch; Fiscal Year: 2007
    ..abstract_text> ..
  4. Epigenetics, Stem Cells, and Cancer
    Rudolf Jaenisch; Fiscal Year: 2010
    ..Aim 3 will use nuclear transplantation as a criterion to define the genetic and epigenetic alterations of the cancer cell genome that interfere with reversion to pluripotency. ..
  5. Epigenetics, Stem Cells, and Cancer
    Rudolf Jaenisch; Fiscal Year: 2007
    ..Aim 3 will use nuclear transplantation as a criterion to define the genetic and epigenetic alterations of the cancer cell genome that interfere with reversion to pluripotency. ..
  6. DNA METHYLATION, GENE REGULATION, AND CANCER
    Rudolf Jaenisch; Fiscal Year: 2005
    ..To investigate a possible causal relation between methylation and gene control we will compare gene expression in matched cell lines where due to inducible Dnmtl deletion the genome is either normal or hypomethylated. ..