title: Identification of novel genes and networks governing hematopoietic stem cell development.
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.
authors: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.
authors: Tianxu
authors: T
authors: Han
authors: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.
authors: Chao-Shun
authors: CS
authors: Yang
authors: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.
authors: Kung-Yen
authors: KY
authors: Chang
authors: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.
authors: Danhua
authors: D
authors: Zhang
authors: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.|Division of Neonatology, Rady Children's Hospital-San Diego, San Diego, CA, USA.
authors: Farhad B
authors: FB
authors: Imam
authors: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA trana@ucsd.edu.|Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Tariq M
authors: 0000-0001-9558-5766
authors: TM
authors: Rana
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D019295:Computational Biology; D053595:Embryonic Stem Cells / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D051379:Mice; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D015027:Zebrafish / Q000235:genetics
keywords: RNAi; directed differentiation; embryonic stem cells; hematopoietic stem cells