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Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6, that efficiently induces endothelial-like precursor cells, with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1, and Prominin1 within a global endothelial transcription program. Emergent hematopoietic cells possess nascent hematopoietic stem cell gene-expression profiles and cell-surface phenotypes. After transgene silencing and reaggregation culture, the specified cells generate hematopoietic colonies in vitro. Thus, we show that a simple combination of transcription factors is sufficient to induce a complex, dynamic, and multistep developmental program in vitro. These findings provide insights into the specification of definitive hemogenesis and a platform for future development of patient-specific stem and progenitor cells, as well as more-differentiated blood products.
Copyright © 2013 Elsevier Inc. All rights reserved.PMID: 23770078Funding information
This work was supported by:
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NHLBI NIH HHS, United States
Grant ID: R01 HL058739
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NHLBI NIH HHS, United States
Grant ID: K08 HL111330
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NIGMS NIH HHS, United States
Grant ID: R01 GM098316
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NHLBI NIH HHS, United States
Grant ID: T32 HL007824
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NHLBI NIH HHS, United States
Grant ID: 5K08HL111330
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NHLBI NIH HHS, United States
Grant ID: 5T32HL007824-15
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NIDDK NIH HHS, United States
Grant ID: R01DK088541
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NIDDK NIH HHS, United States
Grant ID: R01 DK088541
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NIGMS NIH HHS, United States
Grant ID: P50 GM071558
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NIGMS NIH HHS, United States
Grant ID: R01GM098316
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NICHD NIH HHS, United States
Grant ID: T32 HD075735
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