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Identification of novel genes and networks governing hematopoietic stem cell development
Author(s) -
Han Tianxu,
Yang ChaoShun,
Chang KungYen,
Zhang Danhua,
Imam Farhad B,
Rana Tariq M
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201642395
Subject(s) - library science , medicine , medical school , medical education , computer science
Hematopoietic stem cells ( HSC s) are capable of giving rise to all blood cell lineages throughout adulthood, and the generation of engraftable HSC s from human pluripotent stem cells is a major goal for regenerative medicine. Here, we describe a functional genome‐wide RNA i screen to identify genes required for the differentiation of embryonic stem cell ( ESC ) into hematopoietic stem/progenitor cells ( HSPC s) in vitro . We report the discovery of novel genes important for the endothelial‐to‐hematopoietic transition and subsequently for HSPC specification. High‐throughput sequencing and bioinformatic analyses identified twelve groups of genes, including a set of 351 novel genes required for HSPC specification. As in vivo proof of concept, four of these genes, Ap2a1 , Mettl22 , Lrsam1 , and Hal , are selected for validation, confirmed to be essential for HSPC development in zebrafish and for maintenance of human HSC s. Taken together, our results not only identify a number of novel regulatory genes and pathways essential for HSPC development but also serve as valuable resource for directed differentiation of therapy grade HSPC s using human pluripotent stem cells.