Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

Autor:	She R; Whitehead Institute for Biomedical Research, Cambridge, MA, USA., Fair T; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA., Schaefer NK; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Saunders RA; Whitehead Institute for Biomedical Research, Cambridge, MA, USA; Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA, USA., Pavlovic BJ; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Weissman JS; Whitehead Institute for Biomedical Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute Technology, Cambridge, MA 02142, USA. Electronic address: weissman@wi.mit.edu., Pollen AA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: alex.pollen@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2023 Jul 06; Vol. 186 (14), pp. 2977-2994.e23. Date of Electronic Publication: 2023 Jun 20.
DOI:	10.1016/j.cell.2023.05.043
Abstrakt:	Comparative studies of great apes provide a window into our evolutionary past, but the extent and identity of cellular differences that emerged during hominin evolution remain largely unexplored. We established a comparative loss-of-function approach to evaluate whether human cells exhibit distinct genetic dependencies. By performing genome-wide CRISPR interference screens in human and chimpanzee pluripotent stem cells, we identified 75 genes with species-specific effects on cellular proliferation. These genes comprised coherent processes, including cell-cycle progression and lysosomal signaling, which we determined to be human-derived by comparison with orangutan cells. Human-specific robustness to CDK2 and CCNE1 depletion persisted in neural progenitor cells and cerebral organoids, supporting the G1-phase length hypothesis as a potential evolutionary mechanism in human brain expansion. Our findings demonstrate that evolutionary changes in human cells reshaped the landscape of essential genes and establish a platform for systematically uncovering latent cellular and molecular differences between species. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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