Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies | Zendy

Barbara Mair | Zendy; Jelena Tomić | Zendy; San. Masud | Zendy; Peter J. Tonge | Zendy; Alexander Weiß | Zendy; Matej Ušaj | Zendy; Amy H.Y. Tong | Zendy; Jamie J. Kwan | Zendy; Kevin R. Brown | Zendy; Emily Titus | Zendy; Michael Atkins | Zendy; Katherine Chan | Zendy; Lise N. Munsie | Zendy; Andrea Habsid | Zendy; Hong Han | Zendy; Marion Kennedy | Zendy; Brenda Cohen | Zendy; Gordon Keller | Zendy; Jason Moffat | Zendy

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Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies

Author(s) -

Barbara Mair,

Jelena Tomić,

San. Masud,

Peter J. Tonge,

Alexander Weiß,

Matej Ušaj,

Amy H.Y. Tong,

Jamie J. Kwan,

Kevin R. Brown,

Emily Titus,

Michael Atkins,

Katherine Chan,

Lise N. Munsie,

Andrea Habsid,

Hong Han,

Marion Kennedy,

Brenda Cohen,

Gordon Keller,

Jason Moffat

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.02.041

Subject(s) - induced pluripotent stem cell , biology , crispr , gene , computational biology , context (archaeology) , genetics , genome , stem cell , cellular differentiation , regenerative medicine , embryonic stem cell , microbiology and biotechnology , paleontology

Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically cataloging essential genes (EGs) that are indispensable for hPSC fitness, defined as cell reproduction in this study. To map essential genetic determinants of hPSC fitness, we performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and laminin to identify EGs. Among these, we found FOXH1 and VENTX, genes that encode transcription factors previously implicated in stem cell biology, as well as an uncharacterized gene, C22orf43/DRICH1. hPSC EGs are substantially different from other human model cell lines, and EGs in hPSCs are highly context dependent with respect to different growth substrates. Our CRISPR screens establish parameters for genome-wide screens in hPSCs, which will facilitate the characterization of unappreciated genetic regulators of hPSC biology.

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