Evidence map›Paper›PMID 34711655›Full record

ArticleGenes & development2021

Integrated loss- and gain-of-function screens define a core network governing human embryonic stem cell behavior.

Kamila Naxerova, Bruno Di Stefano, Jessica L Makofske, Emma V Watson, Marit A de Kort, Timothy D Martin, Mohammed Dezfulian, Dominik Ricken, Eric C Wooten, Mitzi I Kuroda and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed, 22 citations in OpenAlex.

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  13. Cell state-dependent chromatin targeting in NUT carcinoma.bioRxiv : the preprint server for biology · 2023
    Article
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  15. Article
  16. Article
  17. Genetic Engineering of Immune Evasive Stem Cell-Derived Islets.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Review
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

12 authors at 4 institutions in 1 country.

Kamila NaxerovaDivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Bruno Di StefanoDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Jessica L MakofskeDivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Emma V WatsonDivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Marit A de KortDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Timothy D MartinDivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Mohammed DezfulianDivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Dominik RickenCenter for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Eric C WootenDivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Mitzi I KurodaDivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Konrad HochedlingerDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Stephen J ElledgeDivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Harvard University · USBrigham and Women's Hospital · USHoward Hughes Medical Institute · USMassachusetts General Hospital · US

Funding

PROJECT 4: Somatic evolution of the hematopoietic system in cardiovascular diseaseP01HL142494 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Matthias Nahrendorf · 2019 to 2026
$19.5M
Ubiquitin Mediated Proteolysis and Cell Cycle ControlR01AG011085 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JEFFREY W HARPER · 1993 to 2026
$10.9M
Epigenetic regulation of transcriptional programmingR35GM126944 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI KURODA, MITZI I · 2018 to 2022
$3.3M
Illuminating the evolutionary history of colorectal cancer metastasis: basic principles and clinical applicationsR37CA225655 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI NAXEROVA, KAMILA · 2018 to 2024
$3.0M
Comprehensive analysis of epigenetic regulators in their native chromatin contextR01GM101958 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI KURODA, MITZI I · 2012 to 2018
$2.4M
Analysis of the Mammalian DNA Damage ResponseR01CA234600 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELLEDGE, STEPHEN J · 2019 to 2023
$2.0M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA234600NCI NIH HHS R37 CA225655NHLBI NIH HHS P01 HL142494NIA NIH HHS R01 AG011085NIGMS NIH HHS R01 GM101958NIGMS NIH HHS R35 GM126944
6 · The paper itself

Abstract

Understanding the genetic control of human embryonic stem cell function is foundational for developmental biology and regenerative medicine. Here we describe an integrated genome-scale loss- and gain-of-function screening approach to identify genetic networks governing embryonic stem cell proliferation and differentiation into the three germ layers. We identified a deep link between pluripotency maintenance and survival by showing that genetic alterations that cause pluripotency dissolution simultaneously increase apoptosis resistance. We discovered that the chromatin-modifying complex SAGA and in particular its subunit TADA2B are central regulators of pluripotency, survival, growth, and lineage specification. Joint analysis of all screens revealed that genetic alterations that broadly inhibit differentiation across multiple germ layers drive proliferation and survival under pluripotency-maintaining conditions and coincide with known cancer drivers. Our results show the power of integrated multilayer genetic screening for the robust mapping of complex genetic networks.

Indexed as

Human Embryonic Stem CellsCell DifferentiationEmbryonic Stem CellsGain of Function MutationGerm LayersHumansgenetic screeninggerm layer formationhuman embryonic stem cells

Identifiers

PMID34711655
PMCPMC8559676
OpenAlexW3209100268

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.