Evidence map›Paper›PMID 41233591›Full record

ArticleEMBO reports2025

A primordial germ cell-like-cell platform enables CRISPRi screen for epigenetic fertility modifiers.

Liangdao Li, Jingyi Gao, Dain Yi, Alex P Sheft, John C Schimenti, Xinbao Ding

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Research Progress of Histone Deacetylase and Its Inhibitors in Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2026
    Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Liangdao Li *Cornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY, 14853, USA.ORCID 0000-0001-9266-5103
Jingyi GaoCornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY, 14853, USA.
Dain YiCornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY, 14853, USA.ORCID 0009-0002-0769-153X
Alex P SheftCornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY, 14853, USA.
John C SchimentiCornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY, 14853, USA. jcs92@cornell.edu.ORCID 0000-0002-7294-1876
Xinbao Ding *Cornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY, 14853, USA.ORCID 0000-0001-5941-4898

Funding

Project IIIP50HD096723 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI John C Schimenti · 2019 to 2026
$15.0M
Identification and Functional Validation of Human Infertility AllelesR01HD082568 · NICHD · CORNELL UNIVERSITY · PI SCHIMENTI, JOHN C · 2015 to 2024
$6.0M
HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 1P50HD096723New York State Stem Cell Science (NYSTEM) C30293GGNew York State Stem Cell Science (NYSTEM) CO29155NICHD NIH HHS P50 HD096723NICHD NIH HHS R01 HD082568
6 · The paper itself

Abstract

Primordial germ cells (PGCs) are the precursors of gametes, and the ability to derive PGC-like cells (PGCLCs) from pluripotent stem cells has transformed germline research. A key limitation remains producing PGCLCs in sufficient numbers for large-scale applications. Here, we show that overexpression of Nanog plus three PGC master regulators - Prdm1, Prdm14, and Tfap2c - in mouse epiblast-like cells and formative embryonic stem cells yields abundant and highly enriched PGCLCs without costly recombinant cytokines. Nanog enhances the PGC regulatory network, suppresses somatic differentiation, and stabilizes PGCLC fate. Transcriptomically, these PGCLCs are developmentally more advanced than cytokine-induced counterparts and can be sustained long-term or differentiated into spermatogonia-like cells. Using this platform, we conduct a CRISPRi screen of 701 epigenetic genes to identify those needed for PGCLC formation. Downregulation of Ncor2, a histone deacetylase (HDAC) recruiter, has the greatest impact. Additionally, the HDAC inhibitors valproic acid and sodium butyrate suppress PGCLC formation and sperm counts of in utero-exposed animals. This work establishes a scalable system for functional screening of genes that influence germline development.

Indexed as

CRISPR-Cas SystemsEpigenesis, GeneticFertilityGerm CellsAnimalsCell DifferentiationDNA-Binding ProteinsFemaleMaleMiceNanog Homeobox ProteinPositive Regulatory Domain I-Binding Factor 1Repressor ProteinsRNA-Binding ProteinsTranscription Factor AP-2Transcription FactorsDNA-Binding ProteinsNanog Homeobox ProteinNanog protein, mousePositive Regulatory Domain I-Binding Factor 1Prdm14 protein, mousePrdm1 protein, mouseRepressor ProteinsRNA-Binding ProteinsTfap2c protein, mouseTranscription Factor AP-2Transcription FactorsCRISPRiEpigenomeFertilityHistone Deacetylase InhibitionPGCLCs

Identifiers

PMID41233591
PMCPMC12678824

What OpenQuestion holds

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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.