Evidence map›Paper›PMID 41237780›Full record

ArticleStem cell reports2025

Benchmarking and optimizing Perturb-seq in differentiating human pluripotent stem cells.

Sushama Sivakumar, Yihan Wang, Sean C Goetsch, Vrushali Pandit, Lei Wang, Huan Zhao, Anjana Sundarrajan, Daniel Armendariz, Chikara Takeuchi, Minnie Deng and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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  5. Article
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  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors.

Sushama SivakumarDepartment of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yihan WangCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sean C GoetschDepartment of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Vrushali PanditDepartment of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lei WangCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Huan ZhaoCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Anjana SundarrajanCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Daniel ArmendarizCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Chikara TakeuchiCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Minnie DengDepartment of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Mpathi NzimaCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Wei-Chen ChenDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ashley E DederichDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lauretta El HayekDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Taosha GaoCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ashlesha GogateDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Kiran KaurDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hyung Bum KimCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Melissa K McCoyDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hanspeter NiederstrasserDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Seiya OuraDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Carlos A Pinzon-ArteagaDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Menaka SanghviDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Daniel A SchmitzDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Leqian YuDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yanfeng ZhangQuantitative Biomedical Research Center, Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Qinbo ZhouQuantitative Biomedical Research Center, Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.
W Lee KrausCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lin XuQuantitative Biomedical Research Center, Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jun WuDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Bruce A PosnerDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Maria H ChahrourDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Gary C HonCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; Lyda Hill Department of Bioinformatics, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: gary.hon@utsouthwestern.edu.
Nikhil V MunshiDepartment of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: nikhil.munshi@utsouthwestern.edu.

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Kathryn Ann O'Donnell · 2010 to 2026
$53.7M
Multiscale functional characterization of genomic variation in human developmental disordersUM1HG011996 · NHGRI · UT SOUTHWESTERN MEDICAL CENTER · PI Gary Chung Hon, WILLIAM Lee KRAUS · 2021 to 2026
$10.5M
Developing vectors for potent and selective manipulation of cardiac rhythmR01HL172898 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI NIKHIL Vilas MUNSHI · 2025 to 2026
$1.1M
NCI NIH HHS P30 CA142543NHGRI NIH HHS UM1 HG011996NHLBI NIH HHS R01 HL172898
6 · The paper itself

Abstract

Perturb-seq is a powerful approach to systematically assess how genes and enhancers impact the molecular and cellular pathways of development and disease. However, technical challenges have limited its application in stem-cell-based systems. Here, we benchmarked Perturb-seq across multiple CRISPRi modalities, on diverse genomic targets, in multiple human pluripotent stem cells, during directed differentiation to multiple lineages, and across multiple single guide RNA (sgRNA) delivery systems. To ensure cost-effective production of large-scale Perturb-seq datasets as part of the Impact of Genomic Variants on Function (IGVF) consortium, our optimized protocol dynamically assesses experiment quality across the weeks-long procedure. Our analysis of 1,996,260 sequenced cells across benchmarking datasets reveals shared regulatory networks linking disease-associated enhancers and genes with downstream targets during cardiomyocyte differentiation. This study establishes open tools and resources for interrogating genome function during stem cell differentiation.

Indexed as

Cell DifferentiationPluripotent Stem CellsBenchmarkingCRISPR-Cas SystemsGene Regulatory NetworksHigh-Throughput Nucleotide SequencingHumansMyocytes, CardiacRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas SystemscardiomyocytesCRISPR/Cas9human pluripotent stem cellsneural progenitor cellsPerturb-seqsingle-cell genomics

Identifiers

PMID41237780
PMCPMC12744838

What OpenQuestion holds

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Registered trials

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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.