Stuart H Orkin

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival
    Deeann Wallis
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Development 130:221-32. 2003
  2. pmc A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal
    Guang Hu
    Howard Hughes Medical Institute, Department of Genetics, Division of Genetics, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 23:837-48. 2009
  3. pmc Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine
    Jonghwan Kim
    Department of Pediatric Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Howard Hughes Medical Institute, Boston, MA 02115, USA
    Genome Med 3:75. 2011
  4. pmc Musings on genome medicine: enzyme-replacement therapy of the lysosomal storage diseases
    David G Nathan
    Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Genome Med 1:114. 2009
  5. pmc Musings on genome medicine: the slow but inexorable process of medical care reform in the United States
    David G Nathan
    Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Genome Med 1:94. 2009
  6. pmc Musings on genome medicine: Hepatitis C
    David G Nathan
    Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Genome Med 2:4. 2010
  7. pmc Unraveling the transcriptional network controlling ES cell pluripotency
    Sridhar Rao
    Division of Hematology Oncology, Children s Hospital and the Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Genome Biol 7:230. 2006
  8. ncbi request reprint Stem cells down under-ISSCR 2007
    Stuart H Orkin
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital Boston, Boston, MA 02115, USA
    Cell Stem Cell 1:271-6. 2007
  9. pmc Hematopoiesis: an evolving paradigm for stem cell biology
    Stuart H Orkin
    Division of Hematology Oncology, Children s Hospital Boston and the Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 132:631-44. 2008
  10. pmc Rb and hematopoiesis: stem cells to anemia
    Carl R Walkley
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Division of Hematology Oncology and Stem Cell Program, Children s Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA
    Cell Div 3:13. 2008

Detail Information

Publications114 found, 100 shown here

  1. ncbi request reprint The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival
    Deeann Wallis
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Development 130:221-32. 2003
    ..Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death...
  2. pmc A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal
    Guang Hu
    Howard Hughes Medical Institute, Department of Genetics, Division of Genetics, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 23:837-48. 2009
    ..Our screen has implicated over 100 new genes in ES cell self-renewal, and illustrates the power of RNAi and forward genetics for the systematic study of self-renewal...
  3. pmc Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine
    Jonghwan Kim
    Department of Pediatric Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Howard Hughes Medical Institute, Boston, MA 02115, USA
    Genome Med 3:75. 2011
    ....
  4. pmc Musings on genome medicine: enzyme-replacement therapy of the lysosomal storage diseases
    David G Nathan
    Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Genome Med 1:114. 2009
    ..Preventive strategies involving carrier detection should be a priority toward the successful management of these conditions...
  5. pmc Musings on genome medicine: the slow but inexorable process of medical care reform in the United States
    David G Nathan
    Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Genome Med 1:94. 2009
    ....
  6. pmc Musings on genome medicine: Hepatitis C
    David G Nathan
    Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Genome Med 2:4. 2010
    ..The only current approach for end-stage disease is liver transplant, which ironically does not cure the condition, and thus poses a clinical dilemma in the face of liver-donor shortage...
  7. pmc Unraveling the transcriptional network controlling ES cell pluripotency
    Sridhar Rao
    Division of Hematology Oncology, Children s Hospital and the Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Genome Biol 7:230. 2006
    ..Recent work provides new insights into ES cell pluripotency and delineates separate transcriptional pathways in ES cells for maintenance of the undifferentiated state and for self-renewal...
  8. ncbi request reprint Stem cells down under-ISSCR 2007
    Stuart H Orkin
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital Boston, Boston, MA 02115, USA
    Cell Stem Cell 1:271-6. 2007
    ..Here we review some of the newest findings in an effort to convey the energy and excitement of the meeting and the tempo of stem cell science...
  9. pmc Hematopoiesis: an evolving paradigm for stem cell biology
    Stuart H Orkin
    Division of Hematology Oncology, Children s Hospital Boston and the Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 132:631-44. 2008
    ....
  10. pmc Rb and hematopoiesis: stem cells to anemia
    Carl R Walkley
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Division of Hematology Oncology and Stem Cell Program, Children s Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA
    Cell Div 3:13. 2008
    ....
  11. ncbi request reprint Hematopoiesis and stem cells: plasticity versus developmental heterogeneity
    Stuart H Orkin
    Division of Hematology and Oncology, Dana Farber Cancer Institute and Children s Hospital, Department of Pediatrics, Harvard Medical School and the Howard Hughes Medical Institute, Boston, MA 02115, USA
    Nat Immunol 3:323-8. 2002
    ..In considering these findings, we draw a distinction here between the plasticity of adult stem cells and the heterogeneity of stem cell types that pre-exist within tissues...
  12. doi request reprint Chromatin connections to pluripotency and cellular reprogramming
    Stuart 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...
  13. pmc Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A
    Jian Xu
    Division of Hematology Oncology, Boston Children s Hospital and Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 110:6518-23. 2013
    ..Our findings provide important insights into the mechanistic roles of BCL11A in HbF silencing and clues for therapeutic targeting of BCL11A in β-hemoglobinopathies...
  14. ncbi request reprint Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1
    Shireen Saleque
    Division of Hematology Oncology, Children s Hospital Boston, Boston, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 27:562-72. 2007
    ..Lineage-restricted deployment of these cofactors through interaction with Gfi proteins controls hematopoietic differentiation...
  15. pmc Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation
    BORIS G WILSON
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital Boston, Harvard Medical School, MA 02115, USA
    Cancer Cell 18:316-28. 2010
    ..Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss...
  16. ncbi request reprint Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells
    Hanno Hock
    Division of Hematology Oncology, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 431:1002-7. 2004
    ..Thus, Gfi-1 is essential to restrict HSC proliferation and to preserve HSC functional integrity...
  17. pmc Insights into GATA-1-mediated gene activation versus repression via genome-wide chromatin occupancy analysis
    Ming Yu
    Department of Pediatric Hematology Oncology, Children s Hospital Boston and Dana Farber Cancer Institute, Harvard Medical School, MA 02115, USA
    Mol Cell 36:682-95. 2009
    ..These data provide insights into GATA-1-mediated gene regulation in vivo...
  18. doi request reprint Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A
    Vijay G Sankaran
    Division of Hematology Oncology, Children s Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 322:1839-42. 2008
    ..BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders...
  19. pmc Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis
    Jan Henning Klusmann
    Division of Hematology Oncology, Children s Hospital, Boston, Massachusetts 02115, USA
    Genes Dev 24:1659-72. 2010
    ..Our study underscores context-dependent requirements during oncogenesis, and explains resistance to transformation of ostensibly similar adult progenitors...
  20. pmc Polycomb repressive complex 2 is required for MLL-AF9 leukemia
    Tobias Neff
    Dana Farber Children s Hospital Cancer Center, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:5028-33. 2012
    ..Manipulating PRC2 function may be of therapeutic benefit in AML...
  21. doi request reprint An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level
    Daniel E Bauer
    Division of Hematology Oncology, Boston Children s Hospital, Boston, MA 02115, USA
    Science 342:253-7. 2013
    ..We propose the GWAS-marked BCL11A enhancer represents an attractive target for therapeutic genome engineering for the β-hemoglobinopathies. ..
  22. pmc Translational isoforms of FOG1 regulate GATA1-interacting complexes
    Jonathan W Snow
    Division of Hematology Oncology, Children s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 284:29310-9. 2009
    ....
  23. pmc Polycomb repressive complex 2 regulates normal development of the mouse heart
    Aibin He
    Department of Cardiology, Children s Hospital Boston, MA, USA
    Circ Res 110:406-15. 2012
    ..Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27, which establishes H3K27me3 repressive epigenetic marks that promote tissue-specific differentiation by silencing ectopic gene programs...
  24. pmc A single cis element maintains repression of the key developmental regulator Gata2
    Jonathan W Snow
    Division of Hematology Oncology, Children s Hospital Boston, Boston, Massachusetts, United States of America
    PLoS Genet 6:e1001103. 2010
    ..These studies reveal how an individual cis element establishes a normal developmental program via regulating specific steps in the mechanism by which a critical transcription factor is repressed...
  25. pmc GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis
    Aaron N Chang
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:9237-42. 2002
    ..On the basis of these and previous reports, we infer that GATA factor dependence is a critical aspect of FOG protein function...
  26. pmc Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage
    Alan B Cantor
    Division of Pediatric Hematology Oncology, Children s Hospital Boston, Boston, MA 02115, USA
    J Exp Med 205:611-24. 2008
    ..They also provide evidence for lineage instability during early stages of hematopoietic lineage commitment...
  27. pmc Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development
    Samuel G Katz
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:14030-5. 2003
    ....
  28. pmc Sumoylation regulates interaction of FOG1 with C-terminal-binding protein (CTBP)
    Jonathan W Snow
    Division of Hematology Oncology, Children s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 285:28064-75. 2010
    ..Post-translational modification of FOG1 may contribute to control of co-occupancy by CTBP family members, the NuRD complex, and GATA1 at differentially regulated genes...
  29. pmc Transcriptional silencing of {gamma}-globin by BCL11A involves long-range interactions and cooperation with SOX6
    Jian Xu
    Children s Hospital Boston, Massachusetts 02115, USA
    Genes Dev 24:783-98. 2010
    ..Our findings provide insight into the mechanism of BCL11A action and new clues for the developmental gene regulatory programs that function at the beta-globin locus...
  30. pmc TiF1-gamma plays an essential role in murine hematopoiesis and regulates transcriptional elongation of erythroid genes
    Xiaoying Bai
    Stem Cell Program, Children s Hospital Boston, Boston, MA 02115, USA
    Dev Biol 373:422-30. 2013
    ..Our study therefore demonstrates that TIF1γ plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved...
  31. pmc Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing
    Jian Xu
    Division of Hematology Oncology, Children s Hospital Boston and Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 334:993-6. 2011
    ..Thus, interference with HbF silencing by manipulation of a single target protein is sufficient to reverse SCD...
  32. pmc The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis
    David G Ransom
    Division of Hematology Oncology, Children s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    PLoS Biol 2:E237. 2004
    ..Our results establish a major role for this transcriptional intermediary factor in the differentiation of hematopoietic cells in vertebrates...
  33. pmc TIF1gamma controls erythroid cell fate by regulating transcription elongation
    Xiaoying Bai
    Howard Hughes Medical Institute, Boston, MA 02115, USA
    Cell 142:133-43. 2010
    ..Our study establishes a mechanism for regulating tissue cell fate and differentiation through transcription elongation...
  34. pmc Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment
    Carl R Walkley
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Division of Hematology Oncology and Stem Cell Program, Children s Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 129:1081-95. 2007
    ..Therefore, RB extrinsically regulates HSCs by maintaining the capacity of the BM to support normal hematopoiesis and HSCs...
  35. pmc miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia
    Jan Henning Klusmann
    Children s Hospital Boston, Massachusetts 02115, USA
    Genes Dev 24:478-90. 2010
    ..Thus, we propose miR-125b-2 as a positive regulator of megakaryopoiesis and an oncomiR involved in the pathogenesis of trisomy 21-associated megakaryoblastic leukemia...
  36. pmc Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells
    Xiaohua Shen
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, and Harvard Medical School, Boston, MA 02115, USA
    Cell 139:1303-14. 2009
    ..Our results demonstrate that dynamic regulation of Polycomb complex activity orchestrated by JMJ balances self-renewal and differentiation, highlighting the involvement of chromatin dynamics in cell-fate transitions...
  37. ncbi request reprint Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo
    Hanna K A Mikkola
    Department of Hematology Oncology, Children s Hospital, Boston, MA, USA
    Blood 101:508-16. 2003
    ..Although CD41 is commonly referred to as megakaryocyte-platelet integrin in adult hematopoiesis, these results implicate a wider role for CD41 during murine ontogeny...
  38. ncbi request reprint Developmental stage-selective effect of somatically mutated leukemogenic transcription factor GATA1
    Zhe Li
    Division of Hematology Oncology, Childrens Hospital, Boston, Massachusetts 02115, USA
    Nat Genet 37:613-9. 2005
    ....
  39. pmc MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets
    Zhen Shao
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Genome Biol 13:R16. 2012
    ..The quantitative binding differences inferred by MAnorm showed strong correlation with both the changes in expression of target genes and the binding of cell type-specific regulators...
  40. pmc Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis
    Vijay G Sankaran
    Division of Hematology Oncology, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 22:463-75. 2008
    ..Our work demonstrates how these seemingly disparate pathways play a role in coordinately regulating cellular differentiation...
  41. pmc A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs
    Jonghwan Kim
    Department of Pediatric Oncology, Children s Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cell 143:313-24. 2010
    ..The apparent similarity of cancer and ES cell signatures reflects, in large part, the pervasive nature of Myc regulatory networks...
  42. pmc Differential roles of Sall4 isoforms in embryonic stem cell pluripotency
    Sridhar Rao
    Dana Farber Cancer Institute, Department of Pediatric Oncology, Boston, MA, USA
    Mol Cell Biol 30:5364-80. 2010
    ..Sall4a and Sall4b collaborate in maintenance of the pluripotent state but play distinct roles. Our work is novel in establishing such isoform-specific differences in ES cells...
  43. ncbi request reprint Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart
    Sean M Wu
    Division of Hematology Oncology, Children s Hospital, Boston, MA 02115, USA
    Cell 127:1137-50. 2006
    ..5(+) cells from mouse embryos and demonstrated their capacity for bipotential differentiation in vivo. Taken together, these results support the existence of a common precursor for cardiovascular lineages in the mammalian heart...
  44. pmc GATA-2 reinforces megakaryocyte development in the absence of GATA-1
    Zan Huang
    Division of Hematology and Oncology, Northwestern University, Lurie Research Building 5 113, Chicago, IL 60611, USA
    Mol Cell Biol 29:5168-80. 2009
    ..Moreover, our data reveal that overexpression of GATA-2 facilitates aberrant megakaryopoiesis...
  45. ncbi request reprint Transcriptional regulation of erythropoiesis: an affair involving multiple partners
    Alan B Cantor
    Division of Hematology Oncology, Department of Pediatrics, Children s Hospital Boston and the Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Oncogene 21:3368-76. 2002
    ..This provides a possible mechanism by which dysregulated expression of hematopoietic transcription factors leads to lineage maturation arrest in leukemias...
  46. ncbi request reprint Haematopoietic stem cells retain long-term repopulating activity and multipotency in the absence of stem-cell leukaemia SCL/tal-1 gene
    Hanna K A Mikkola
    Department of Pediatric Oncology, Children s Hospital and the Dana Farber Cancer Institute, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
    Nature 421:547-51. 2003
    ..These findings contrast with lineage choice mechanisms, in which the identity of haematopoietic lineages requires continuous transcription factor expression...
  47. ncbi request reprint Functional overlap of GATA-1 and GATA-2 in primitive hematopoietic development
    Yuko Fujiwara
    Children s Hospital, Enders 760, 300 Longwood Ave, Boston, MA 02115, USA
    Blood 103:583-5. 2004
    ..Thus, the function of GATA-1 and GATA-2 overlaps at the yolk sac stage. Moreover, a GATA factor, either GATA-1 or GATA-2, is required to initiate blood formation in the embryo...
  48. pmc Distinct domains of the GATA-1 cofactor FOG-1 differentially influence erythroid versus megakaryocytic maturation
    Alan B Cantor
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 22:4268-79. 2002
    ..Importantly, we find that distinct regions of FOG-1 differentially influence erythroid versus megakaryocyte maturation. As such, we propose that FOG-1 may modulate the fate of a bipotential erythroid/megakaryocytic precursor cell...
  49. pmc ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex
    Zhe Li
    Division of Hematology Oncology, Children s Hospital Boston, Boston, MA 02115, USA
    Cancer Cell 12:542-58. 2007
    ..Given the increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of preclinical models...
  50. pmc PRC2 directly methylates GATA4 and represses its transcriptional activity
    Aibin He
    Department of Cardiology, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 26:37-42. 2012
    ..Our results reveal a new mechanism of PRC2-mediated transcriptional repression in which PRC2 methylates a transcription factor to inhibit its transcriptional activity...
  51. pmc Gata4 is necessary for normal pulmonary lobar development
    Kate G Ackerman
    Division of Genetics, Brigham and Women s Hospital, Harvard Medical School New Research Building 458, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Am J Respir Cell Mol Biol 36:391-7. 2007
    ..Fog2 and Gata4 in the early pulmonary mesenchyme participate in patterning the secondary bronchus of the accessory lobe...
  52. pmc Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease
    Carl R Walkley
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Division of Hematology Oncology, Boston, MA 02115, USA
    Genes Dev 22:1662-76. 2008
    ..Due to the strong similarity between murine osteosarcoma and human osteosarcoma in this model, this should provide a valuable platform for addressing the molecular genetics of osteosarcoma and for developing novel therapeutic strategies...
  53. pmc X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affecting DNA binding rather than FOG-1 interaction
    Channing Yu
    Division of Hematology Oncology, Department of Medicine, Children s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
    Blood 100:2040-5. 2002
    ..This is also the first example of beta-thalassemia in humans caused by a mutation in an erythroid transcription factor...
  54. pmc Requirement of Nanog dimerization for stem cell self-renewal and pluripotency
    Jianlong Wang
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, and Howard Hughes Medical Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:6326-31. 2008
    ..Our results demonstrate that Nanog-Nanog homodimerization is a critical aspect of its function promoting stem cell pluripotency...
  55. pmc Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells
    Carl R Walkley
    Department of Pediatric Oncology, Dana Farber Cancer Institute, and Division of Hematology Oncology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:9057-62. 2006
    ..These studies demonstrate that Rb is not intrinsically required for self-renewal and multilineage differentiation of adult HSCs...
  56. pmc A functional element necessary for fetal hemoglobin silencing
    Vijay G Sankaran
    Department of Medicine, Children s Hospital Boston, Boston, MA 02115, USA
    N Engl J Med 365:807-14. 2011
    ..Although recent studies have uncovered trans-acting factors necessary for this regulation, limited insight has been gained into the cis-regulatory elements involved...
  57. pmc Decoding hematopoietic specificity in the helix-loop-helix domain of the transcription factor SCL/Tal-1
    Thorsten M Schlaeger
    Department of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA
    Mol Cell Biol 24:7491-502. 2004
    ..Our data highlight the functional complexity of bHLH proteins, provide mechanistic insight into SCL function, and strongly support the existence of an active SCL/LMO2-containing multiprotein complex in early hematopoietic cells...
  58. pmc Combinatorial assembly of developmental stage-specific enhancers controls gene expression programs during human erythropoiesis
    Jian Xu
    Division of Hematology Oncology, Children s Hospital Boston and Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 23:796-811. 2012
    ....
  59. ncbi request reprint Specification of astrocytes by bHLH protein SCL in a restricted region of the neural tube
    Yuko Muroyama
    Department of Pediatric Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nature 438:360-3. 2005
    ..They further indicate that acquisition of embryonic glial subtype identity might be regulated by genetic interactions between SCL and the transcription factor Olig2 in the ventral neural tube...
  60. ncbi request reprint Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2
    Sergei G Tevosian
    Division of Hematology and Oncology, Children s Hospital, Harvard Medical School, Boston, MA, USA
    Development 129:4627-34. 2002
    ..These results indicate that GATA4 and FOG2 and their physical interaction are required for normal gonadal development...
  61. doi request reprint Use of in vivo biotinylation to study protein-protein and protein-DNA interactions in mouse embryonic stem cells
    Jonghwan Kim
    Division of Hematology Oncology, Department of Pediatric Oncology, Children s Hospital and the Dana Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA
    Nat Protoc 4:506-17. 2009
    ..The system setup takes approximately 50 d to complete, and it takes another approximately 15 d and approximately 3 d to perform affinity purification of protein complexes and bioChIP, respectively...
  62. doi request reprint TEL-AML1 corrupts hematopoietic stem cells to persist in the bone marrow and initiate leukemia
    Jeffrey W Schindler
    Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell Stem Cell 5:43-53. 2009
    ..Our work shows that stem cells are susceptible to subversion by weak oncogenes that can subtly alter their molecular program to provide a latent reservoir for the accumulation of further mutations...
  63. pmc Oct4 dependence of chromatin structure within the extended Nanog locus in ES cells
    Dana N Levasseur
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA
    Genes Dev 22:575-80. 2008
    ..We analyzed gene expression, chromatin occupancy, and higher-order chromatin structure throughout this gene locus and found that expression of the reprogramming factor Oct4 is required to maintain its integrity...
  64. pmc EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency
    Xiaohua Shen
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 32:491-502. 2008
    ..Ezh1 partially complements Ezh2 in executing pluripotency during ESC differentiation, suggesting that cell-fate transitions require epigenetic specificity...
  65. ncbi request reprint Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)-dependent window during hematopoietic stem-cell development
    Thorsten M Schlaeger
    Division of Hematology Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 105:3871-4. 2005
    ..These results indicate that the SCL-dependent phase of HSC development ends before Tie2Cre-mediated gene ablation becomes effective...
  66. doi request reprint Glimpses of the epigenetic landscape
    Xiaohua Shen
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cell Stem Cell 4:1-2. 2009
    ..Revealing chromatin-state maps in model cell types will provide an important framework in which to consider epigenetic controls at molecular and systematic levels...
  67. ncbi request reprint Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis
    Neil P Rodrigues
    Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Boston, MA 02129, USA
    Blood 106:477-84. 2005
    ..Thus, GATA-2 dose regulates adult stem-cell homeostasis by affecting select aspects of stem cell function...
  68. pmc Site-directed, virus-free, and inducible RNAi in embryonic stem cells
    Jianlong Wang
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Stem Cell Institute, and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:20850-5. 2007
    ..This site-directed, virus-free, and tet-inducible RNAi system, designated as SDVFi RNAi in our study, presents an efficient option for controlled gene silencing in ES cells...
  69. pmc Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis
    Trista E North
    Stem Cell Program and Division of Hematology Oncology, Children s Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 447:1007-11. 2007
    ..The conserved role for PGE2 in the regulation of vertebrate HSC homeostasis indicates that modulation of the prostaglandin pathway may facilitate expansion of HSC number for therapeutic purposes...
  70. doi request reprint Advances in the understanding of haemoglobin switching
    Vijay G Sankaran
    Division of Hematology Oncology, Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
    Br J Haematol 149:181-94. 2010
    ....
  71. pmc Context-dependent function of "GATA switch" sites in vivo
    Jonathan W Snow
    Division of Hematology Oncology, Children s Hospital Boston, Boston, MA, USA
    Blood 117:4769-72. 2011
    ..8 kb site was not required to initiate or maintain repression. These analyses reveal qualitatively distinct functions of 2 GATA motif-containing regions in vivo...
  72. pmc ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling
    Jochen C Hartner
    Department of Pediatric Oncology, Dana Farber Cancer Institute Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 10:109-15. 2009
    ....
  73. pmc Phosphorylation of Gata1 at serine residues 72, 142, and 310 is not essential for hematopoiesis in vivo
    Heather M Rooke
    Division of Hematology Oncology, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Blood 107:3527-30. 2006
    ..Yet, later stage erythropoiesis was not perturbed. This suggests that any molecular consequences associated with loss of phosphorylation at residues 72, 142, and 310 can be compensated for in the in vivo environment...
  74. ncbi request reprint A protein interaction network for pluripotency of embryonic stem cells
    Jianlong Wang
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA
    Nature 444:364-8. 2006
    ..This tight protein network seems to function as a cellular module dedicated to pluripotency...
  75. ncbi request reprint Coregulation of GATA factors by the Friend of GATA (FOG) family of multitype zinc finger proteins
    Alan B Cantor
    Division of Pediatric Hematology Oncology, Children s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
    Semin Cell Dev Biol 16:117-28. 2005
    ..In this review, we will discuss the identification and characterization of FOG proteins, their role in human disease, and recent studies that shed new light on their function and regulation...
  76. pmc Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo
    Channing Yu
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    J Exp Med 195:1387-95. 2002
    ..Mice lacking the ability to produce eosinophils should prove useful in ascertaining the role of eosinophils in a variety of inflammatory or allergic disorders...
  77. pmc Developmental and species-divergent globin switching are driven by BCL11A
    Vijay G Sankaran
    Division of Hematology Oncology, Children s Hospital Boston and Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 460:1093-7. 2009
    ..By comparing the ontogeny of beta-globin gene regulation in mice and humans, we have shown that alterations in the expression of a trans-acting factor constitute a critical driver of gene expression changes during evolution...
  78. ncbi request reprint Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation
    Hanno Hock
    Division of Hematology Oncology, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Immunity 18:109-20. 2003
    ..Thus, Gfi-1 not only promotes differentiation of neutrophils but also antagonizes traits of the alternate monocyte/macrophage program...
  79. pmc Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo
    Samuel G Katz
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, U SA
    Mol Cell Biol 22:3121-8. 2002
    ..Thus, despite conservation of the FOG-CtBP interaction site, the in vivo function of FOG-1 in erythroid development is not affected by its inability to interact with the corepressor CtBP...
  80. pmc Musings on genome medicine: gene therapy
    David G Nathan
    Dana Farber Cancer Institute, Binney Street, Boston, MA 02115, USA
    Genome Med 1:38. 2009
    ..The field may be poised to move forward more rapidly, but many barriers have yet to be surmounted...
  81. ncbi request reprint Transforming acidic coiled-coil protein 3 (TACC3) controls friend of GATA-1 (FOG-1) subcellular localization and regulates the association between GATA-1 and FOG-1 during hematopoiesis
    Mireia Garriga-Canut
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
    J Biol Chem 279:23597-605. 2004
    ....
  82. ncbi request reprint The SWI/SNF complex--chromatin and cancer
    Charles W M Roberts
    Dana Farber Cancer Institute and Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 4:133-42. 2004
  83. ncbi request reprint Placenta as a site for hematopoietic stem cell development
    Hanna K A Mikkola
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital, Boston, Mass 02115, USA
    Exp Hematol 33:1048-54. 2005
    ....
  84. pmc The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages
    Shireen Saleque
    Department of Pediatric Oncology, Children s Hospital, Dana Farber Cancer Institute, Harvard Medical School, and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
    Genes Dev 16:301-6. 2002
    ..Myelopoiesis is normal. Therefore, Gfi-1b is an essential transcriptional regulator of erythroid and megakaryocyte development...
  85. pmc Musings on genome medicine: the Obama effect redux
    David G Nathan
    Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Genome Med 1:86. 2009
    ....
  86. ncbi request reprint Zinc-finger transcription factor Gfi-1: versatile regulator of lymphocytes, neutrophils and hematopoietic stem cells
    Hanno Hock
    Division of Hematology Oncology, Children s Hospital, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Curr Opin Hematol 13:1-6. 2006
    ..Here we review recent studies pertaining to Gfi-1 and its cell context specific functions in hematopoietic development...
  87. ncbi request reprint Chipping away at the embryonic stem cell network
    Stuart H Orkin
    Dana Farber Cancer Institute and Children s Hospital Boston, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
    Cell 122:828-30. 2005
    ..2005) demonstrate frequent promoter co-occupancy at numerous target genes. As they discuss in this issue of Cell, their findings indicate the presence of a complex network of autoregulatory and feedforward loops in human ES cells...
  88. ncbi request reprint The placenta is a niche for hematopoietic stem cells
    Christos Gekas
    Department of Pediatric Oncology, Dana Farber Cancer Institute and, Childrens Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Dev Cell 8:365-75. 2005
    ..Importantly, the placental HSC pool is not explained by rare circulating HSCs, which appear later. These data support an important, but unappreciated, role for the placenta in establishing the mammalian definitive hematopoietic system...
  89. pmc Musings on genome medicine: cancer genetics and the promise of effective treatment
    David G Nathan
    Dana Farber Cancer Institute, Binney Street, Boston, MA 02115, USA
    Genome Med 1:49. 2009
    ..Although there are serious technological and cost hurdles to surmount and resistance and continued mutation will be a constant problem, the way is clear to rational therapy...
  90. ncbi request reprint A critical role for eosinophils in allergic airways remodeling
    Alison A Humbles
    Department of Pediatrics, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Science 305:1776-9. 2004
    ..These data suggest that eosinophils contribute substantially to airway remodeling but are not obligatory for allergen-induced lung dysfunction, and support an important role for eosinophil-targeted therapies in chronic asthma...
  91. pmc Musings on genome medicine: cholesterol and coronary artery disease
    David G Nathan
    Dana Farber Cancer Institute, Binney Street, Boston, MA 02115, USA
    Genome Med 1:60. 2009
    ..Diabetes greatly increases the risk at any cholesterol level. Coronary artery disease and cancer are linked by a common protein - an apoptotic protein that also functions as a regulator of insulin secretion...
  92. ncbi request reprint Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5
    Charles W M Roberts
    Division of Hematology Oncology, Dana Farber Cancer Institute and Children s Hospital, Department of Pediatrics, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA
    Cancer Cell 2:415-25. 2002
    ....
  93. pmc The transcription factor GATA2 regulates differentiation of brown adipocytes
    Judy Tsai
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    EMBO Rep 6:879-84. 2005
    ..Collectively, these results show that GATA2 functions to suppress brown adipocyte differentiation, whereas reduction of GATA2 promotes brown adipogenesis...
  94. pmc Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival
    Hanno Hock
    Division of Hematology Oncology, Children s Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 18:2336-41. 2004
    ..Thus, we establish Tel/Etv6 as a selective and essential regulator of postembryonic HSCs...
  95. ncbi request reprint The use of altered specificity mutants to probe specific protein-protein interactions involved in the activation of GATA-1 target genes
    John D Crispino
    Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA
    Methods 26:84-92. 2002
    ..Once altered specificity factors are obtained, a researcher can then proceed to functional assays that address the role of a specific protein-protein interaction...
  96. ncbi request reprint Stem-cell competition
    Stuart H Orkin
    Nature 418:25-7. 2002
  97. ncbi request reprint The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1
    Eric Lecuyer
    Clinical Research Institute of Montreal and from the Departments of Pharmacology, Biochemistry, and Molecular Biology, Universite de Montreal, Quebec, Canada
    Blood 100:2430-40. 2002
    ....
  98. pmc GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-1low mouse mutant
    Anna Rita Migliaccio
    Department of Biomorphology, University G D Annunzio, 66100 Chieti, Italy
    J Exp Med 197:281-96. 2003
    ..These abnormalities, which were mirrored by impaired mast differentiation in vitro, were reversed by retroviral-mediated expression of GATA-1 cDNA. These data indicate an essential role for GATA-1 in mast cell differentiation...
  99. ncbi request reprint Notch signaling requires GATA-2 to inhibit myelopoiesis from embryonic stem cells and primary hemopoietic progenitors
    Renee F de Pooter
    Department of Immunology, University of Toronto, Sunnybrook and Women s Research Institute, 2075 Bayview Avenue, Toronto, Ontario, Canada
    J Immunol 176:5267-75. 2006
    ..Importantly, in the absence of GATA-2, Dll-1-induced signals fail to inhibit commitment to the myeloid fate. Taken together, our results support a role for GATA-2 in allowing Dll-1 to restrict non-T cell lineage differentiation outcomes...
  100. ncbi request reprint The journey of developing hematopoietic stem cells
    Hanna K A Mikkola
    Department of Molecular, Cell and Developmental Biology, Jonsson Comprehensive Cancer Center, Institute for Stem Cell Biology and Medicine, University of California, Los Angeles, CA 90095, USA
    Development 133:3733-44. 2006
    ..Elucidating the interactions between developing HSCs and their niches should facilitate the generation and expansion of HSCs in vitro to exploit their clinical potential...
  101. pmc Phosphatidylinositol 3-kinase/Akt induced by erythropoietin renders the erythroid differentiation factor GATA-1 competent for TIMP-1 gene transactivation
    Zahra Kadri
    Department of d Hématologie, Institute Cochin, INSERM U56, CNRS UMR 8104, Université René Descartes Hospital Cochin, Paris, France
    Mol Cell Biol 25:7412-22. 2005
    ..These findings provide the first example of a chain of coupling mechanisms between the binding of erythropoietin to its receptor and GATA-1-dependent gene expression...