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Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture
Author(s) -
Daniel Michael G.,
Sachs David,
Bernitz Jeffrey M.,
Fstkchyan Yesai,
Rapp Katrina,
Satija Namita,
Law Kenneth,
Patel Foram,
Gomes Andreia M.,
Kim HuenSuk,
Pereira CarlosFilipe,
Chen Benjamin,
Lemischka Ihor R.,
Moore Kateri A.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13621
Subject(s) - reprogramming , haematopoiesis , biology , microbiology and biotechnology , gata2 , stem cell , progenitor cell , transcription factor , population , somatic cell , regenerative medicine , gene , genetics , medicine , environmental health
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 coculture 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. Database Gene expression data are available in the Gene Expression Omnibus (GEO) database under the accession number GSE130361 .