Stuart H. Orkin, MD
Contact Information
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Appointments
Biography
Stuart H. Orkin, MD
Dr. Orkin received his MD in 1972 from Harvard Medical School, followed by postdoctoral research at the National Institutes of Health and clinical training in pediatrics and hematology-oncology at Children's Hospital Boston and DFCI, where he joined the faculty in 1978. Dr. Orkin is a Howard Hughes Medical Institute Investigator and was elected to the 2019-2020 Council of the National Academy of Medicine. Over the past decade, his laboratory has defined critical nuclear regulators of hematopoiesis.
Researcher
Physician
Centers/Programs
Clinical Interests
Pediatric hematology/oncology
Diseases Treated
Fellowship
- Boston Children's Hospital, Pediatric Hematology/Oncology
Residency
- Boston Children's Hospital, Pediatrics
Medical School
- Harvard Medical School
Recent Awards
- Gruber Genetics Prize, Yale, 2021
- Tobias Lecture Award, ISSCR, 2021
- Harrington Prize for Innovation in Medicine, Harrington Discovery Institute and The American Society for Clinical Investigation, 2020
- King Faisal Prize for Medicine, 2020
- AAMC Award for Distinguished Research in Medical Sciences, 2005
- Warren Alpert Foundation Prize, 1993
- Member, Institute of Medicine, 1992
- Member, American Academy of Arts and Sciences, 1992
- Member, National Academy of Sciences, 1991
- Dameshek Award, American Society of Hematology, 1986
Research
Molecular Genetics of Blood Cell Development and Stem Cells
All blood cells arise from committed progenitors, which are descendants of pluripotent hematopoietic stem cells. The goal of our laboratory is to understand how commitment to specific blood lineages is programmed and how cell-specific patterns of gene expression are established. Since gene expression is controlled by nuclear regulatory factors (transcription factors), efforts have centered on identifying those crucial for the development of stem cells or individual lineages. Research encompasses conventional molecular biology and contemporary mouse genetics. Lineage specification and hematopoietic differentiation. Red blood cells and megakaryocytes (which produce platelets) share a common precursor cell. We discovered a transcription factor, GATA1, that participates in the regulation of virtually all red cell (erythroid) and megakaryocyte-specific expressed genes. Expression of GATA1 in progenitors drives cells toward erythroid and megakaryocytic fates. Disruption of the Gata1 gene in mice leads to a failure of maturation of both lineages. In addition to controlling end-stage markers of these lineages, GATA1 influences proliferation and cell death decisions of precursor cells. Using this mouse model to dissect mechanisms of cell differentiation, we have sought to understand how GATA1 functions in transcription. This line of investigation led us to hypothesize and then discover a cofactor required for GATA1's function in these lineages. This novel cofactor, FOG (for friend of GATA1), is also essential for normal red blood cell and megakaryocyte development. Current research focuses on how FOG modulates the function of GATA1 and related factors during hematopoietic and nonhematopoietic cell development. Hematopoiesis-leukemia interface. Remarkably, many genes essential for normal hematopoietic development are involved in chromosomal translocations in human leukemias. This finding reflects perturbation of normal homeostasis by expression of an altered protein or excessive production of an otherwise normal factor. We are studying several transcription factors (e.g., SCL/tal-1, TEL) affected by genetic events in leukemias. Our work is directed toward understanding the normal roles of these transcription factors in hematopoiesis and vascular development. In addition, efforts are ongoing to recreate in mice the common form of childhood leukemia, acute lymphoblastic leukemia, associated with fusion of the TEL and AML1 genes. This animal model will permit improved understanding of the pathogenesis of acute lymphoblastic leukemia and provide a system for testing new therapies.
Research Departments
Publications
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Mechanistic and kinetic insights into transcription factor biology via acute protein depletion. Exp Hematol. 2024 Jun 09; 137:104250. View in: Pubmed
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Matrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions. Nat Commun. 2024 Feb 10; 15(1):1274. View in: Pubmed
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Structural Insights into the DNA-Binding Mechanism of BCL11A: The Integral Role of ZnF6. bioRxiv. 2024 Jan 19. View in: Pubmed
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Transcriptional Repressor BCL11A in Erythroid Cells. Adv Exp Med Biol. 2024; 1459:199-215. View in: Pubmed
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Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche. Nat Commun. 2023 Dec 02; 14(1):7978. View in: Pubmed
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Identifying quantitatively differential chromosomal compartmentalization changes and their biological significance from Hi-C data using DARIC. BMC Genomics. 2023 Oct 13; 24(1):614. View in: Pubmed
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In vivo CRISPR/Cas9 screening identifies Pbrm1 as a regulator of myeloid leukemia development in mice. Blood Adv. 2023 09 26; 7(18):5281-5293. View in: Pubmed
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Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis. Nat Genet. 2023 07; 55(7):1149-1163. View in: Pubmed
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Identifying Quantitatively Differential Chromosomal Compartmentalization Changes and Their Biological Significance from Hi-C data using DARIC. Res Sq. 2023 Apr 28. View in: Pubmed
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Rapid-kinetics degron benchmarking reveals off-target activities and mixed agonism-antagonism of MYB inhibitors. bioRxiv. 2023 Apr 07. View in: Pubmed
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Fetal Hemoglobin Regulation in Beta-Thalassemia. Hematol Oncol Clin North Am. 2023 04; 37(2):301-312. View in: Pubmed
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Leukemia core transcriptional circuitry is a sparsely interconnected hierarchy stabilized by incoherent feed-forward loops. bioRxiv. 2023 Mar 15. View in: Pubmed
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Defining the structure, signals, and cellular elements of the gastric mesenchymal niche. bioRxiv. 2023 Feb 24. View in: Pubmed
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Polycomb deficiency drives a FOXP2-high aggressive state targetable by epigenetic inhibitors. Nat Commun. 2023 01 20; 14(1):336. View in: Pubmed
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Evolution of nanobodies specific for BCL11A. Proc Natl Acad Sci U S A. 2023 01 17; 120(3):e2218959120. View in: Pubmed
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A Cell-Permeant Nanobody-Based Degrader That Induces Fetal Hemoglobin. ACS Cent Sci. 2022 Dec 28; 8(12):1695-1703. View in: Pubmed
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High-efficiency knock-in of degradable tags (dTAG) at endogenous loci in cell lines. Methods Enzymol. 2023; 681:1-22. View in: Pubmed
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Transcriptional Plasticity Drives Leukemia Immune Escape. Blood Cancer Discov. 2022 09 06; 3(5):394-409. View in: Pubmed
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Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells. Cell Chem Biol. 2022 08 18; 29(8):1273-1287.e8. View in: Pubmed
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Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts. Cancer Discov. 2022 07 06; 12(7):1760-1781. View in: Pubmed
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CD49b identifies functionally and epigenetically distinct subsets of lineage-biased hematopoietic stem cells. Stem Cell Reports. 2022 07 12; 17(7):1546-1560. View in: Pubmed
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Hypoxic, glycolytic metabolism is a vulnerability of B-acute lymphoblastic leukemia-initiating cells. Cell Rep. 2022 04 26; 39(4):110752. View in: Pubmed
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Congenital anemia reveals distinct targeting mechanisms for master transcription factor GATA1. Blood. 2022 04 21; 139(16):2534-2546. View in: Pubmed
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Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis. Cell Rep. 2022 04 05; 39(1):110587. View in: Pubmed
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A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia. Genes Dev. 2022 03 01; 36(5-6):368-389. View in: Pubmed
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Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer. Genes Dev. 2022 01 01; 36(1-2):38-52. View in: Pubmed
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Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture. Nat Commun. 2021 10 29; 12(1):6241. View in: Pubmed
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Mapping the evolving landscape of super-enhancers during cell differentiation. Genome Biol. 2021 09 15; 22(1):269. View in: Pubmed
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Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis. Cell Stem Cell. 2021 11 04; 28(11):1922-1935.e5. View in: Pubmed
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A unified model of human hemoglobin switching through single-cell genome editing. Nat Commun. 2021 08 17; 12(1):4991. View in: Pubmed
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Reactivation of a developmentally silenced embryonic globin gene. Nat Commun. 2021 07 21; 12(1):4439. View in: Pubmed
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Indispensable epigenetic control of thymic epithelial cell development and function by polycomb repressive complex 2. Nat Commun. 2021 06 24; 12(1):3933. View in: Pubmed
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Author Correction: Transcription factor competition at the ?-globin promoters controls hemoglobin switching. Nat Genet. 2021 Apr; 53(4):586. View in: Pubmed
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Transcription factor competition at the ?-globin promoters controls hemoglobin switching. Nat Genet. 2021 04; 53(4):511-520. View in: Pubmed
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MOLECULAR MEDICINE: Found in Translation. Med. 2021 02 12; 2(2):122-136. View in: Pubmed
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ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit. J Biol Chem. 2020 12 18; 295(51):17738-17751. View in: Pubmed
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Arid4b is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit. J Biol Chem. 2020 Oct 15. View in: Pubmed
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A saturating mutagenesis CRISPR-Cas9-mediated functional genomic screen identifies cis- and trans-regulatory elements of Oct4 in murine ESCs. J Biol Chem. 2020 11 20; 295(47):15797-15809. View in: Pubmed
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Enhancer dependence of cell-type-specific gene expression increases with developmental age. Proc Natl Acad Sci U S A. 2020 09 01; 117(35):21450-21458. View in: Pubmed
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An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells. Cell. 2020 Jun 25; 181(7):1693-1694. View in: Pubmed
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An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells. Cell. 2020 06 11; 181(6):1410-1422.e27. View in: Pubmed
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Multiplexed capture of spatial configuration and temporal dynamics of locus-specific 3D chromatin by biotinylated dCas9. Genome Biol. 2020 03 05; 21(1):59. View in: Pubmed
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Live-animal imaging of native haematopoietic stem and progenitor cells. Nature. 2020 02; 578(7794):278-283. View in: Pubmed
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Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation. Nat Genet. 2020 02; 52(2):138-145. View in: Pubmed
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CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis. Genome Biol. 2019 09 09; 20(1):192. View in: Pubmed
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BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells. Nature. 2019 08; 572(7771):676-680. View in: Pubmed
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Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis. Nat Genet. 2019 07; 51(7):1149-1159. View in: Pubmed
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TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network. Mol Cell. 2019 06 20; 74(6):1148-1163.e7. View in: Pubmed
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Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA. Mol Cell. 2019 05 02; 74(3):542-554.e5. View in: Pubmed
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Yap1 safeguards mouse embryonic stem cells from excessive apoptosis during differentiation. Elife. 2018 12 18; 7. View in: Pubmed
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Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer. Cell Rep. 2018 12 18; 25(12):3504-3518.e6. View in: Pubmed
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CRISPR-SURF: discovering regulatory elements by deconvolution of CRISPR tiling screen data. Nat Methods. 2018 12; 15(12):992-993. View in: Pubmed
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PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia. J Exp Med. 2018 12 03; 215(12):3094-3114. View in: Pubmed
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FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity. J Biol Chem. 2018 12 21; 293(51):19797-19811. View in: Pubmed
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Emerging Genetic Therapy for Sickle Cell Disease. Annu Rev Med. 2019 01 27; 70:257-271. View in: Pubmed
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Polycomb Repressive Complex 2 is essential for development and maintenance of a functional TEC compartment. Sci Rep. 2018 09 25; 8(1):14335. View in: Pubmed
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Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids. PLoS Biol. 2018 08; 16(8):e2004986. View in: Pubmed
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Author Correction: High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2018 08; 560(7717):E26. View in: Pubmed
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Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells. Sci Rep. 2018 05 22; 8(1):8001. View in: Pubmed
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Mapping the Mouse Cell Atlas by Microwell-Seq. Cell. 2018 05 17; 173(5):1307. View in: Pubmed
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The Polycomb-Dependent Epigenome Controls ß Cell Dysfunction, Dedifferentiation, and Diabetes. Cell Metab. 2018 Jun 05; 27(6):1294-1308.e7. View in: Pubmed
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14q32 and let-7 microRNAs regulate transcriptional networks in fetal and adult human erythroblasts. Hum Mol Genet. 2018 04 15; 27(8):1411-1420. View in: Pubmed
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Integrated design, execution, and analysis of arrayed and pooled CRISPR genome-editing experiments. Nat Protoc. 2018 May; 13(5):946-986. View in: Pubmed
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Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch. Cell. 2018 04 05; 173(2):430-442.e17. View in: Pubmed
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Dissecting super-enhancer hierarchy based on chromatin interactions. Nat Commun. 2018 03 05; 9(1):943. View in: Pubmed
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Mapping the Mouse Cell Atlas by Microwell-Seq. Cell. 2018 02 22; 172(5):1091-1107.e17. View in: Pubmed
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Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS. Cancer Cell. 2018 03 12; 33(3):386-400.e5. View in: Pubmed
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Regulation of embryonic haematopoietic multipotency by EZH1. Nature. 2018 01 25; 553(7689):506-510. View in: Pubmed
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Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci. Proc Natl Acad Sci U S A. 2017 Dec 26; 114(52):E11257-E11266. View in: Pubmed
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Recent progress in understanding and manipulating haemoglobin switching for the haemoglobinopathies. Br J Haematol. 2018 03; 180(5):630-643. View in: Pubmed
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First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor. Proc Natl Acad Sci U S A. 2017 09 19; 114(38):10125-10130. View in: Pubmed
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PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer. Cancer Res. 2017 09 01; 77(17):4613-4625. View in: Pubmed
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Gene correction of HAX1 reversed Kostmann disease phenotype in patient-specific induced pluripotent stem cells. Blood Adv. 2017 Jun 13; 1(14):903-914. View in: Pubmed
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A molecular roadmap for induced multi-lineage trans-differentiation of fibroblasts by chemical combinations. Cell Res. 2017 06; 27(6):843. View in: Pubmed
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A molecular roadmap for induced multi-lineage trans-differentiation of fibroblasts by chemical combinations. Cell Res. 2017 06; 27(6):842. View in: Pubmed
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The 2017 ASPHO distinguished career award goes to Holcombe E. Grier, MD. Pediatr Blood Cancer. 2017 06; 64 Suppl 1. View in: Pubmed
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Erythropoietin signaling regulates heme biosynthesis. Elife. 2017 05 29; 6. View in: Pubmed
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Challenges and emerging directions in single-cell analysis. Genome Biol. 2017 05 08; 18(1):84. View in: Pubmed
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Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells. Stem Cells. 2017 07; 35(7):1773-1785. View in: Pubmed
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EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent. Elife. 2017 04 10; 6. View in: Pubmed
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Functional interrogation of non-coding DNA through CRISPR genome editing. Methods. 2017 May 15; 121-122:118-129. View in: Pubmed
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Transcription control by the ENL YEATS domain in acute leukaemia. Nature. 2017 03 09; 543(7644):270-274. View in: Pubmed
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Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci. Nat Genet. 2017 Apr; 49(4):625-634. View in: Pubmed
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Characterization of genomic deletion efficiency mediated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells. J Biol Chem. 2017 02 10; 292(6):2556. View in: Pubmed
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A molecular roadmap for induced multi-lineage trans-differentiation of fibroblasts by chemical combinations. Cell Res. 2017 03; 27(3):386-401. View in: Pubmed
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The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Nat Immunol. 2017 02; 18(2):184-195. View in: Pubmed
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Strict in vivo specificity of the Bcl11a erythroid enhancer. Blood. 2016 11 10; 128(19):2338-2342. View in: Pubmed
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CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell types. Genome Biol. 2016 09 29; 17(1):201. View in: Pubmed
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Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype. Cell Rep. 2016 09 20; 16(12):3181-3194. View in: Pubmed
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Chronic Myelogenous Leukemia- Initiating Cells Require Polycomb Group Protein EZH2. Cancer Discov. 2016 11; 6(11):1237-1247. View in: Pubmed
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Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype. J Clin Invest. 2016 10 03; 126(10):3868-3878. View in: Pubmed
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Single-Cell Transcript Profiles Reveal Multilineage Priming in Early Progenitors Derived from Lgr5(+) Intestinal Stem Cells. Cell Rep. 2016 08 23; 16(8):2053-2060. View in: Pubmed
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Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease. Am J Hematol. 2016 09; 91(9):931-7. View in: Pubmed
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Analyzing CRISPR genome-editing experiments with CRISPResso. Nat Biotechnol. 2016 07 12; 34(7):695-7. View in: Pubmed
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The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 07 11; 30(1):183. View in: Pubmed
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Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis. J Exp Med. 2016 07 25; 213(8):1479-96. View in: Pubmed
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Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis. Exp Hematol. 2016 10; 44(10):947-63. View in: Pubmed
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An Achilles' Heel for MLL-Rearranged Leukemias: Writers and Readers of H3 Lysine 36 Dimethylation. Cancer Discov. 2016 07; 6(7):700-2. View in: Pubmed
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Hemoglobin genetics: recent contributions of GWAS and gene editing. Hum Mol Genet. 2016 10 01; 25(R2):R99-R105. View in: Pubmed
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Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-ß signalling. Nat Commun. 2016 06 22; 7:12047. View in: Pubmed
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MEDICINE. Paying for future success in gene therapy. Science. 2016 May 27; 352(6289):1059-61. View in: Pubmed
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Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells. Cell. 2016 Jun 02; 165(6):1389-1400. View in: Pubmed
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Corrigendum: LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice. Nat Commun. 2016 Apr 20; 7:11467. View in: Pubmed
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Interferon-a signaling promotes embryonic HSC maturation. Blood. 2016 07 14; 128(2):204-16. View in: Pubmed
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The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 04 11; 29(4):574-586. View in: Pubmed
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Customizing the genome as therapy for the ß-hemoglobinopathies. Blood. 2016 05 26; 127(21):2536-45. View in: Pubmed
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High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016 Mar 03; 531(7592):53-8. View in: Pubmed
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Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia. Cell Rep. 2016 Mar 01; 14(8):1953-65. View in: Pubmed
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Recent advances in globin research using genome-wide association studies and gene editing. Ann N Y Acad Sci. 2016 03; 1368(1):5-10. View in: Pubmed
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Serum-Based Culture Conditions Provoke Gene Expression Variability in Mouse Embryonic Stem Cells as Revealed by Single-Cell Analysis. Cell Rep. 2016 Feb 02; 14(4):956-965. View in: Pubmed
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Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin. Science. 2016 Jan 15; 351(6270):285-9. View in: Pubmed
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Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease. Blood. 2016 Feb 18; 127(7):839-48. View in: Pubmed
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Polycomb Repressive Complex 2 Is a Barrier to KRAS-Driven Inflammation and Epithelial-Mesenchymal Transition in Non-Small-Cell Lung Cancer. Cancer Cell. 2016 Jan 11; 29(1):17-31. View in: Pubmed
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Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis. Dev Cell. 2016 Jan 11; 36(1):9-23. View in: Pubmed
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Corrigendum: Failure to replicate the STAP cell phenomenon. Nature. 2016 Mar 17; 531(7594):400. View in: Pubmed
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Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity. Proc Natl Acad Sci U S A. 2015 Dec 29; 112(52):15988-93. View in: Pubmed
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LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice. Nat Commun. 2015 Dec 02; 6:10116. View in: Pubmed
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SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2. Nat Med. 2015 Dec; 21(12):1491-6. View in: Pubmed
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The LSD1 Family of Histone Demethylases and the Pumilio Posttranscriptional Repressor Function in a Complex Regulatory Feedback Loop. Mol Cell Biol. 2015 Dec; 35(24):4199-211. View in: Pubmed
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Failure to replicate the STAP cell phenomenon. Nature. 2015 Sep 24; 525(7570):E6-9. View in: Pubmed
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Hematopoietic stem cells develop in the absence of endothelial cadherin 5 expression. Blood. 2015 Dec 24; 126(26):2811-20. View in: Pubmed
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BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature. 2015 Nov 12; 527(7577):192-7. View in: Pubmed
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Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr Opin Genet Dev. 2015 Aug; 33:62-70. View in: Pubmed
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Functional footprinting of regulatory DNA. Nat Methods. 2015 Oct; 12(10):927-30. View in: Pubmed
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EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression. Blood. 2015 Oct 15; 126(16):1930-9. View in: Pubmed
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PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells. Cell Rep. 2015 Sep 01; 12(9):1456-70. View in: Pubmed
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Inactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model. Exp Hematol. 2015 Nov; 43(11):930-935.e6. View in: Pubmed
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miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction. Mol Ther. 2015 Sep; 23(9):1465-74. View in: Pubmed
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Regulation of Peripheral Nerve Myelin Maintenance by Gene Repression through Polycomb Repressive Complex 2. J Neurosci. 2015 Jun 03; 35(22):8640-52. View in: Pubmed
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Embryonic stem cells as sources of donor-independent platelets. J Clin Invest. 2015 Jun; 125(6):2261-3. View in: Pubmed
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BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations. J Clin Invest. 2015 Jun; 125(6):2363-8. View in: Pubmed
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Opposing Roles for the lncRNA Haunt and Its Genomic Locus in Regulating HOXA Gene Activation during Embryonic Stem Cell Differentiation. Cell Stem Cell. 2015 May 07; 16(5):504-16. View in: Pubmed
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The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability. Sci Signal. 2015 Apr 14; 8(372):ra34. View in: Pubmed
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Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC emergence. J Exp Med. 2015 May 04; 212(5):633-48. View in: Pubmed
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2014 William Allan Award: A hematologist's pursuit of hemoglobin genetics. Am J Hum Genet. 2015 Mar 05; 96(3):354-60. View in: Pubmed
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Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling. Elife. 2015 Feb 25; 4. View in: Pubmed
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Functional Proteomic Analysis of Repressive Histone Methyltransferase Complexes Reveals ZNF518B as a G9A Regulator. Mol Cell Proteomics. 2015 Jun; 14(6):1435-46. View in: Pubmed
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Developmental control of polycomb subunit composition by GATA factors mediates a switch to non-canonical functions. Mol Cell. 2015 Jan 22; 57(2):304-316. View in: Pubmed
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Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence. EMBO J. 2015 Mar 12; 34(6):759-77. View in: Pubmed
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Generation of genomic deletions in mammalian cell lines via CRISPR/Cas9. J Vis Exp. 2015 Jan 03; (95):e52118. View in: Pubmed
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Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc Natl Acad Sci U S A. 2014 Dec 23; 111(51):E5564-73. View in: Pubmed
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Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis. Genome Biol. 2014 Dec 03; 15(12):525. View in: Pubmed
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Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution. Science. 2014 Nov 21; 346(6212):1007-12. View in: Pubmed
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A comparative encyclopedia of DNA elements in the mouse genome. Nature. 2014 Nov 20; 515(7527):355-64. View in: Pubmed
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Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production. Genes Dev. 2014 Dec 01; 28(23):2597-612. View in: Pubmed
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Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing JAK2-V617F. J Exp Med. 2014 Oct 20; 211(11):2213-30. View in: Pubmed
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TMEM14C is required for erythroid mitochondrial heme metabolism. J Clin Invest. 2014 Oct; 124(10):4294-304. View in: Pubmed
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Characterization of genomic deletion efficiency mediated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells. J Biol Chem. 2014 08 01; 289(31):21312-24. View in: Pubmed
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Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. Cell. 2014 Apr 24; 157(3):549-64. View in: Pubmed
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Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation. J Exp Med. 2014 May 05; 211(5):909-27. View in: Pubmed
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Corepressor Rcor1 is essential for murine erythropoiesis. Blood. 2014 May 15; 123(20):3175-84. View in: Pubmed
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Analysis of chromatin-state plasticity identifies cell-type-specific regulators of H3K27me3 patterns. Proc Natl Acad Sci U S A. 2014 Jan 21; 111(3):E344-53. View in: Pubmed
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Calpain 2 activation of P-TEFb drives megakaryocyte morphogenesis and is disrupted by leukemogenic GATA1 mutation. Dev Cell. 2013 Dec 23; 27(6):607-20. View in: Pubmed
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Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity. Mol Cell. 2014 01 09; 53(1):32-48. View in: Pubmed
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GATA1s induces hyperproliferation of eosinophil precursors in Down syndrome transient leukemia. Leukemia. 2014 Jun; 28(6):1259-70. View in: Pubmed
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Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner. Cell Stem Cell. 2014 Jan 02; 14(1):68-80. View in: Pubmed
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An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science. 2013 Oct 11; 342(6155):253-7. View in: Pubmed
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Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy. Leukemia. 2014 Mar; 28(3):577-88. View in: Pubmed
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Delineating the mixed lineage leukemia gene expression network in hematopoietic stem cells. Proc Natl Acad Sci U S A. 2013 Jul 16; 110(29):11670-1. View in: Pubmed
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The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med. 2013 Jan 01; 3(1):a011643. View in: Pubmed
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Musings on genome medicine: enzyme-replacement therapy of the lysosomal storage diseases. Genome Med. 2009 Dec 09; 1(12):114. View in: Pubmed
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Musings on genome medicine: cholesterol and coronary artery disease. Genome Med. 2009 Jun 08; 1(6):60. View in: Pubmed
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Musings on genome medicine: abuse of genetic tests. Genome Med. 2009 Feb 16; 1(2):18. View in: Pubmed
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Requirement of Nanog dimerization for stem cell self-renewal and pluripotency. Proc Natl Acad Sci U S A. 2008 Apr 29; 105(17):6326-31. View in: Pubmed
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Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res. 2004 Oct; 14(10B):2162-8. View in: Pubmed
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The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis. PLoS Biol. 2004 Aug; 2(8):E237. View in: Pubmed
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Combinatorial interactions of serpent, lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis. Proc Natl Acad Sci U S A. 2003 Sep 30; 100(20):11451-6. View in: Pubmed
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Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature. 2003 Jul 31; 424(6948):561-5. View in: Pubmed
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Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood. 2003 Jan 15; 101(2):508-16. View in: Pubmed
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The search for the hemangioblast. J Hematother Stem Cell Res. 2002 Feb; 11(1):9-17. View in: Pubmed
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