Induction of a Hemogenic Program in Mouse Fibroblasts
Pereira, C.F., Chang, B., Qiu, J., Niu, X., Papatsenko, D., Hendry, C.E., Clark, N.R., Nomura-Kitabayashi, A., Kovacic, J.C., Ma'ayan, A., Schaniel, C., Lemischka, I.R., Moore, K.
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/specifying hematopoietic stem cell gene expression profiles and cell surface phenotypes. After transgene silencing and reaggreagtion culture the specified cells generate hematopoietic colonies in vitro. Thus, we have shown that a simple combination of transcription factors is sufficient to induce a complex, dynamic and multi-step developmental program in vitro. These findings provide insights into the specification of definitive hemogenesis and a platform for future development of patient-specific stem/progenitor cells as well as more differentiated blood products.
Pereira, C.F., Chang, B., Qiu, J., Niu, X., Papatsenko, D., Hendry, C.E., Clark, N.R., Nomura-Kitabayashi, A., Kovacic, J.C., Ma'ayan, A., Schaniel, C., Lemischka, I.R., Moore, K. "Induction of a Hemogenic Program in Mouse Fibroblasts" Cell Stem Cell (2013): 205–18