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Comparative RNAi Screens in Isogenic Human Stem Cells Reveal SMARCA4 as a Differential Regulator. | LitMetric

Comparative RNAi Screens in Isogenic Human Stem Cells Reveal SMARCA4 as a Differential Regulator.

Stem Cell Reports

Medical Faculty and University Hospital Carl Gustav Carus, UCC Section Medical Systems Biology, TU Dresden, 01307 Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg and German Research Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany; National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Electronic address:

Published: May 2019

AI Article Synopsis

Article Abstract

Large-scale RNAi screens are a powerful approach to identify functions of genes in a cell-type-specific manner. For model organisms, genetically identical (isogenic) cells from different cell types are readily available, making comparative studies meaningful. However, large-scale screens in isogenic human primary cells remain challenging. Here, we show that RNAi screens are possible in genetically identical human stem cells, using induced pluripotent stem cells as intermediates. The screens revealed SMARCA4 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4) as a stemness regulator, while balancing differentiation distinctively for each cell type. SMARCA4 knockdown in hematopoietic stem and progenitor cells caused impaired self-renewal in vitro and in vivo with skewed myeloid differentiation; whereas, in neural stem cells, it impaired self-renewal while biasing differentiation toward neural lineage, through combinatorial SWI/SNF subunit assembly. Our findings pose a powerful approach for deciphering human stem cell biology and attribute distinct roles to SMARCA4 in stem cell maintenance.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523874PMC
http://dx.doi.org/10.1016/j.stemcr.2019.03.012DOI Listing

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