title: Direct reprogramming of murine fibroblasts to hematopoietic progenitor cells.
abstract: Recent reports have shown that somatic cells, under appropriate culture conditions, could be directly reprogrammed to cardiac, hepatic, or neuronal phenotype by lineage-specific transcription factors. In this study, we demonstrate that both embryonic and adult somatic fibroblasts can be efficiently reprogrammed to clonal multilineage hematopoietic progenitors by the ectopic expression of the transcription factors ERG, GATA2, LMO2, RUNX1c, and SCL. These reprogrammed cells were stably expanded on stromal cells and possessed short-term reconstitution ability in vivo. Loss of p53 function facilitated reprogramming to blood, and p53(-/-) reprogrammed cells efficiently generated erythroid, megakaryocytic, myeloid, and lymphoid lineages. Genome-wide analyses revealed that generation of hematopoietic progenitors was preceded by the appearance of hemogenic endothelial cells expressing endothelial and hematopoietic genes. Altogether, our findings suggest that direct reprogramming could represent a valid alternative approach to the differentiation of embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) for disease modeling and autologous blood cell therapies.
authors.affiliation: CRUK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Kiran
authors.initials: K
authors.lastname: Batta
authors.affiliation: CRUK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florkowska
authors.affiliation: CRUK Stem Cell Haematopoiesis Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kouskoff
authors.affiliation: CRUK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. Electronic address: georges.lacaud@cruk.manchester.ac.uk.
authors.forename: Georges
authors.initials: G
authors.lastname: Lacaud
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000502:physiology*; D015870:Gene Expression; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D057026:Induced Pluripotent Stem Cells / Q000502:physiology; D051379:Mice; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D059467:Transcriptome; D014161:Transduction, Genetic
chemical_list: D014157:Transcription Factors