Evidence map›Paper›PMID 30448000›Full record

ArticleCell systems2018

Mapping Cellular Reprogramming via Pooled Overexpression Screens with Paired Fitness and Single-Cell RNA-Sequencing Readout.

Udit Parekh, Yan Wu, Dongxin Zhao, Atharv Worlikar, Neha Shah, Kun Zhang, Prashant Mali

Abstract read
In one paragraph

Article in Cell systems, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing 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

41 citing papers in PubMed.

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  15. Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
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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

7 authors.

Udit ParekhDepartment of Electrical and Computer Engineering, University of California, San Diego, La Jolla, CA, USA.
Yan WuDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Dongxin ZhaoDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Atharv WorlikarDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Neha ShahDepartment of Nanoengineering, University of California, San Diego, La Jolla, CA, USA.
Kun ZhangDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA. Electronic address: kzhang@bioeng.ucsd.edu.
Prashant MaliDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA. Electronic address: pmali@ucsd.edu.

Funding

A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
Next-generation Functional Genetic Screening of Un-screenable TraitsR01HG009285 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT, TAMAYO, PABLO · 2017 to 2020
$4.2M
Improving cell fate conversion by tracking cells and RNA over time and spaceR01HL123755 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IZPISUA BELMONTE, JUAN CARLOS, ZHANG, KUN · 2015 to 2018
$3.0M
Systematic mapping of genetic vulnerabilities in head and neck cancerR01CA222826 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT · 2018 to 2022
$1.8M
Dissecting the interplay of gene regulatory networks and cellular niche on cell fate determinationR01GM123313 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT · 2018 to 2021
$1.2M
NCI NIH HHS R01 CA222826NHGRI NIH HHS R01 HG009285NHLBI NIH HHS R01 HL123755NIEHS NIH HHS R01 ES014811NIGMS NIH HHS R01 GM123313
6 · The paper itself

Abstract

Understanding the effects of genetic perturbations on the cellular state has been challenging using traditional pooled screens, which typically rely on the delivery of a single perturbation per cell and unidimensional phenotypic readouts. Here, we use barcoded open reading frame overexpression libraries coupled with single-cell RNA sequencing to assay cell state and fitness, a technique we call SEUSS (scalable functional screening by sequencing). Using SEUSS, we perturbed hPSCs with a library of developmentally critical transcription factors (TFs) and assayed the impact of TF overexpression on fitness and transcriptomic states. We further leveraged the versatility of the ORF library approach to assay mutant genes and whole gene families. From the transcriptomic responses, we built genetic co-regulatory networks to identify altered gene modules and found that KLF4 and SNAI2 drive opposing effects along the epithelial-mesenchymal transition axis. From the fitness responses, we identified ETV2 as a driver of reprogramming toward an endothelial-like state.

Indexed as

Gene Expression ProfilingGene Regulatory NetworksCell LineCellular ReprogrammingEpithelial-Mesenchymal TransitionHumansKruppel-Like Factor 4MaleSequence Analysis, RNASingle-Cell AnalysisTranscription FactorsKLF4 protein, humanKruppel-Like Factor 4Transcription Factorscellular reprogrammingORF overexpressionpluripotent stem cellssingle-cell screens

Identifiers

PMID30448000
PMCPMC6311450

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.