Induction of a hemogenic program in mouse fibroblasts

Carlos Filipe Pereira, Betty Chang, Jiajing Qiu, Xiaohong Niu, Dmitri Papatsenko, Caroline E. Hendry, Neil R. Clark, Aya Nomura-Kitabayashi, Jason C. Kovacic, Avi Ma'Ayan, Christoph Schaniel, Ihor R. Lemischka, Kateri Moore

    Research output: Contribution to journalArticlepeer-review


    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. © 2013 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)205-218
    Number of pages13
    JournalCell Stem Cell
    Issue number2
    Publication statusPublished - 1 Aug 2013


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