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Inducible Forward Programming of Human Pluripotent Stem Cells to Hemato-endothelial Progenitor Cells with Hematopoietic Progenitor Potential

: Lange, L.; Hoffmann, D.; Schwarzer, A.; Ha, T.-C.; Philipp, F.; Lenz, D.; Morgan, M.; Schambach, A.

Volltext ()

Stem cell reports 14 (2020), Nr.1, S.122-137
ISSN: 2213-6711
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer ITEM ()

Induced pluripotent stem cells (iPSCs) offer a promising platform to model early embryonic developmental processes, to create disease models that can be evaluated by drug screens as well as proof-of-concept experiments for regenerative medicine. However, generation of iPSC-derived hemato-endothelial and hematopoietic progenitor cells for these applications is challenging due to variable and limited cell numbers, which necessitates enormous up-scaling or development of demanding protocols. Here, we unravel the function of key transcriptional regulators SCL, LMO2, GATA2, and ETV2 (SLGE) on early hemato-endothelial specification and establish a fully inducible and stepwise hemato-endothelial forward programming system based on SLGE-regulated overexpression. Regulated induction of SLGE in stable SLGE-iPSC lines drives very efficient generation of large numbers of hemato-endothelial progenitor cells (CD144+/CD73–), which produce hematopoietic progenitor cells (CD45+/CD34+/CD38–/CD45RA−/CD90+/CD49f+) through a gradual process of endothelial-to-hematopoietic transition (EHT).