Identification of novel genes and networks governing hematopoietic stem cell development |
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| Authors: | Tianxu Han Chao‐Shun Yang Kung‐Yen Chang Danhua Zhang Farhad B Imam Tariq M Rana |
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| Institution: | 1. Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA;2. Division of Neonatology, Rady Children's Hospital‐San Diego, San Diego, CA, USA;3. Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA |
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| 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. |
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| Keywords: | directed differentiation embryonic stem cells hematopoietic stem cells RNAi |
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