CRISPR screens in physiologic medium reveal conditionally essential genes in human cells.

Autor:	Rossiter NJ; Morgridge Institute for Research, Madison, WI 53715, USA., Huggler KS; Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA., Adelmann CH; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Keys HR; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Soens RW; Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA., Sabatini DM; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: sabatini@wi.mit.edu., Cantor JR; Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA. Electronic address: jcantor@morgridge.org.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2021 Jun 01; Vol. 33 (6), pp. 1248-1263.e9. Date of Electronic Publication: 2021 Mar 01.
DOI:	10.1016/j.cmet.2021.02.005
Abstrakt:	Forward genetic screens across hundreds of cancer cell lines have started to define the genetic dependencies of proliferating human cells and how these vary by genotype and lineage. Most screens, however, have been carried out in culture media that poorly reflect metabolite availability in human blood. Here, we performed CRISPR-based screens in traditional versus human plasma-like medium (HPLM). Sets of conditionally essential genes in human cancer cell lines span several cellular processes and vary with both natural cell-intrinsic diversity and the combination of basal and serum components that comprise typical media. Notably, we traced the causes for each of three conditional CRISPR phenotypes to the availability of metabolites uniquely defined in HPLM versus conventional media. Our findings reveal the profound impact of medium composition on gene essentiality in human cells, and also suggest general strategies for using genetic screens in HPLM to uncover new cancer vulnerabilities and gene-nutrient interactions. Competing Interests: Declaration of interests J.R.C. and D.M.S. are inventors on a patent application for HPLM (PCT/US2017/061377) assigned to the Whitehead Institute. The remaining authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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