Evidence map›Paper›PMID 33651980›Full record

ArticleCell metabolism2021

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

Nicholas J Rossiter, Kimberly S Huggler, Charles H Adelmann, Heather R Keys, Ross W Soens, David M Sabatini, Jason R Cantor

Open access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
8.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 149 citations in OpenAlex.

  1. 3D Ewing Sarcoma Modeling for Metabolic Studies.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  2. Article
  3. Dual-line Genome-scale CRISPR Screening Enables Robust Target Gene Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 1 country.

Nicholas J RossiterMorgridge Institute for Research, Madison, WI 53715, USA.
Kimberly S HugglerMorgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Charles H AdelmannWhitehead 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.
Heather R KeysWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Ross W SoensMorgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
David M SabatiniWhitehead 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.
Jason R CantorMorgridge 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.
Morgridge Institute for Research · USUniversity of Wisconsin–Madison · USAllen Institute · USMassachusetts Institute of Technology · USWhitehead Institute for Biomedical Research · US

Funding

PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
BIOTECHNOLOGY TRAINING PROGRAMT32GM008349 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FOX, BRIAN G · 1989 to 2019
$22.5M
Institutional Training in the Genomic SciencesT32HG002760 · NHGRI · UNIVERSITY OF WISCONSIN-MADISON · PI Qiongshi Lu · 2003 to 2026
$17.7M
Regulation of the mTOR Pathway By NutrientsR01CA103866 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2004 to 2021
$7.0M
TRANSLATIONAL CONTROL BY RAPAMYCIN-SENSITIVE SIGNALINGR01AI047389 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2000 to 2021
$4.9M
Novel Components of the mTORC1 and mTORC2 PathwaysR37AI047389 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI SABATINI, DAVID M. · 2010 to 2019
$4.8M
Use of Physiologic Media to Study Metabolic Regulation and Requirements in CancerK22CA225864 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI CANTOR, JASON ROBERT · 2019 to 2021
$569k
Genetic identification of novel mTORC1 regulators and homeostatic signaling mechanismsF31CA228241 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ADELMANN, CHARLES HANK · 2018 to 2020
$134k
NCI NIH HHS F31 CA228241NCI NIH HHS K22 CA225864NCI NIH HHS R01 CA103866NHGRI NIH HHS T32 HG002760NIAID NIH HHS R01 AI047389NIAID NIH HHS R37 AI047389NIGMS NIH HHS T32 GM007287NIGMS NIH HHS T32 GM008349
6 · The paper itself

Abstract

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.

Indexed as

CRISPR-Cas SystemsCulture MediaCell Line, TumorHumansCulture Mediaconditional gene essentialityCRISPRgene-nutrient interactiongenetic screenHPLMphysiologic medium

Identifiers

PMID33651980
PMCPMC8172426
OpenAlexW3133635220

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.