Evidence map›Paper›PMID 30995470›Full record

ArticleCell reports2019

Single-Cell RNA-Sequencing-Based CRISPRi Screening Resolves Molecular Drivers of Early Human Endoderm Development.

Ryan M J Genga, Eric M Kernfeld, Krishna M Parsi, Teagan J Parsons, Michael J Ziller, René Maehr

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

57 citing papers in PubMed, 103 citations in OpenAlex.

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  15. The Current Situation and Development Prospect of Whole-Genome Screening.International journal of molecular sciences · 2024
    Review
  16. The genetics and pathogenesis of CAKUT.Nature reviews. Nephrology · 2023
    Review
  17. Review
  18. Article
  19. Article
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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

6 authors at 2 institutions in 2 countries.

Ryan M J GengaProgram in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Eric M KernfeldProgram in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Krishna M ParsiProgram in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Teagan J ParsonsProgram in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Michael J ZillerDepartment of Translational Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
René MaehrProgram in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: rene.maehr@umassmed.edu.
University of Massachusetts Chan Medical School · USMax Planck Institute of Psychiatry · DE

Funding

Humanized Mouse Avatars for T1DU01DK104218 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BREHM, MICHAEL ALLEN, GREINER, DALE LESLIE · 2019 to 2023
$4.5M
Novel humanized mouse model developed from cord blood CD34 positive HSC and autologous iPS cell derived thymusR01AI132963 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BREHM, MICHAEL ALLEN, MAEHR, RENE · 2017 to 2021
$4.4M
Deciphering the molecular basis of T1D in human cells using functional genomicsDP3DK111898 · NIDDK · HARVARD UNIVERSITY · PI CARR, STEVEN A, MAEHR, RENE · 2016 to 2016
$4.2M
NIAID NIH HHS R01 AI132963NIDDK NIH HHS DP3 DK111898NIDDK NIH HHS U01 DK104218
6 · The paper itself

Abstract

Studies in vertebrates have outlined conserved molecular control of definitive endoderm (END) development. However, recent work also shows that key molecular aspects of human END regulation differ even from rodents. Differentiation of human embryonic stem cells (ESCs) to END offers a tractable system to study the molecular basis of normal and defective human-specific END development. Here, we interrogated dynamics in chromatin accessibility during differentiation of ESCs to END, predicting DNA-binding proteins that may drive this cell fate transition. We then combined single-cell RNA-seq with parallel CRISPR perturbations to comprehensively define the loss-of-function phenotype of those factors in END development. Following a few candidates, we revealed distinct impairments in the differentiation trajectories for mediators of TGFβ signaling and expose a role for the FOXA2 transcription factor in priming human END competence for human foregut and hepatic END specification. Together, this single-cell functional genomics study provides high-resolution insight on human END development.

Indexed as

Cell DifferentiationChromatinClustered Regularly Interspaced Short Palindromic RepeatsEndodermHepatocyte Nuclear Factor 3-betaHuman Embryonic Stem CellsHumansPluripotent Stem CellsRNA, Guide, CRISPR-Cas SystemsRNA InterferenceSignal TransductionSingle-Cell AnalysisSmad4 ProteinSOXF Transcription FactorsTranscription FactorsTransforming Growth Factor betaChromatinFOXA2 protein, humanHepatocyte Nuclear Factor 3-betaRNA, Guide, CRISPR-Cas SystemsSmad4 ProteinSMAD4 protein, humanSOX17 protein, humanSOXF Transcription FactorsTranscription FactorsTransforming Growth Factor betachromatin accessibilityCRISPRidCas9-KRABendodermhepatic endodermhuman developmentperturbation screenpluripotent stem cellssingle-cell RNA-seqstem cell differentiation

Identifiers

PMID30995470
PMCPMC6525305
OpenAlexW2936506456

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.