FEBS Lett. 2019 Sep 26. doi: 10.1002/1873-3468.13621. [Epub ahead of print]

Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic co-culture.

Daniel MG^1,2,3, Sachs D^1,2,3, Bernitz JM⁴, Fstkchyan Y^1,3, Rapp K^1,2, Satija N⁵, Law K⁶, Patel F⁵, Gomes AM⁷, Kim HS^1,2,3, Pereira CF⁸, Chen B⁵, Lemischka IR^1,2,9, Moore KA^1,2.

Abstract

Transcription factor (TF)-based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse and human fibroblasts to hemogenic endothelial-like precursors that generate Hematopoietic Stem Progenitor (HSPC)-like cells over time. This conversion is lacking in robustness both in yield and biological function. Herein, we show that inclusion of GFI1 to the reprogramming cocktail significantly expands the HSPC-like population. AFT024 co-culture imparts functional potential to these cells and allows quantification of stem cell frequency. Altogether, we demonstrate an improved human hemogenic induction protocol that could provide a valuable human in vitro model of hematopoiesis for disease modeling and a platform for cell-based therapeutics.