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  • Identification of novel genes and networks governing hematopoietic stem cell development.

Identification of novel genes and networks governing hematopoietic stem cell development.

EMBO reports (2016-11-01)
Tianxu Han, Chao-Shun Yang, Kung-Yen Chang, Danhua Zhang, Farhad B Imam, Tariq M Rana
ABSTRACT

Hematopoietic stem cells (HSCs) are capable of giving rise to all blood cell lineages throughout adulthood, and the generation of engraftable HSCs from human pluripotent stem cells is a major goal for regenerative medicine. Here, we describe a functional genome-wide RNAi screen to identify genes required for the differentiation of embryonic stem cell (ESC) into hematopoietic stem/progenitor cells (HSPCs) 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 HSCs. 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 HSPCs using human pluripotent stem cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hyaluronidase from sheep testes, Type II, lyophilized powder, ≥300 units/mg solid
Sigma-Aldrich
Deoxyribonuclease I from bovine pancreas, Type II, lyophilized powder, Protein ≥80 %, ≥2,000 units/mg protein