title: Induction of a hemogenic program in mouse fibroblasts.
abstract: 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.
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1496, New York, NY 10029, USA. filipe.pereira@mssm.edu
authors.forename: Carlos-Filipe
authors.initials: CF
authors.lastname: Pereira
authors.forename: Betty
authors.initials: B
authors.lastname: Chang
authors.forename: Jiajing
authors.initials: J
authors.lastname: Qiu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Niu
authors.forename: Dmitri
authors.initials: D
authors.lastname: Papatsenko
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Hendry
authors.forename: Neil R
authors.initials: NR
authors.lastname: Clark
authors.forename: Aya
authors.initials: A
authors.lastname: Nomura-Kitabayashi
authors.forename: Jason C
authors.initials: JC
authors.lastname: Kovacic
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
authors.forename: Christoph
authors.initials: C
authors.lastname: Schaniel
authors.forename: Ihor R
authors.initials: IR
authors.lastname: Lemischka
authors.forename: Kateri
authors.initials: K
authors.lastname: Moore
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002449:Cell Aggregation; D019070:Cell Lineage / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014157:Transcription Factors; D049452:Green Fluorescent Proteins