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. 2015 Jul 14;7(11):1388–1402. doi: 10.15252/emmm.201505301

Figure 3. Early hematopoietic development and transprogramming strategies.

Figure 3

During hematopoietic differentiation in vitro, PSCs differentiate through mesodermal cells into cells of hemogenic endothelium capable to form either HSPCs or endothelial cells. This process is regulated by defined transcription factors, such as SCL/TAL, GATA2, MIXL1, T, SOX17, and RUNX1a. Further differentiation of HSPCs gives rise to CLPs or CMPs, respectively. Overexpression of Erg, Gata2, Lmo2, Runx1c, and Scl or Gata2, Gfi1b, cFos, or Etv in murine fibroblasts allows for the direct reprogramming of fibroblasts into HSPCs by a hemogenic endothelium intermediate. Alternatively, murine CMPs can be directly reprogrammed toward HSPCs by overexpression of Run1t1, Hlf, Lmo2, Pbx1, Prdm5, or Zfp37. Moreover, also endothelial cells can be directed toward HSPCs by the expression of FOSB, GFI1, RUNX1, or SPI1, whereas direct induction of HSPCs from PSCs was shown by overexpression of HOXA9, ERG, RORA, MYB, and SOX4. Abbreviations: PSC, pluripotent stem cell; HSPC, hematopoietic stem/progenitor cell; CLP, common lymphoid progenitor; CMP, common myeloid progenitor.