Evidence map›Paper›PMID 41171758›Full record

ArticleCell reports2025

In vivo differentiation of embryonic cells devoid of key reprogramming factors.

Scott E Youlten, Liyun Miao, Caroline Hoppe, Curtis W Boswell, Damir Musaev, Mario Abdelmessih, Damilola Olowookere, Linnea A Weiss, Smita Krishnaswamy, Antonio J Giraldez and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Scott E YoultenDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Liyun MiaoDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Caroline HoppeDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Curtis W BoswellDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Damir MusaevDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Mario AbdelmessihDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Damilola OlowookereDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Linnea A WeissDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Smita KrishnaswamyDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Computer Science, Yale University, New Haven, CT 06510, USA.
Antonio J GiraldezDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: antonio.giraldez@yale.edu.
Valerie A TorniniDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Institute for Society and Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. Electronic address: vtornini@ucla.edu.

Funding

Molecular mechanisms of the maternal to zygotic transitionR35GM122580 · NIGMS · YALE UNIVERSITY · PI Antonio J Giraldez · 2017 to 2026
$8.1M
Deciphering the regulatory code that specifies different cell fates in development using single cell genomicsR01HD100035 · NICHD · YALE UNIVERSITY · PI GIRALDEZ, ANTONIO J, KRISHNASWAMY, SMITA · 2020 to 2024
$2.8M
Mechanisms Regulating Chromatin Organization and Epigenetic MemoryR01HD119238 · NICHD · YALE UNIVERSITY · PI Antonio J Giraldez · 2025 to 2026
$1.2M
Functional analysis of histone modifier Autism Spectrum Disorders risk genes in vertebrate developmentR00HD105001 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie Angela Tornini · 2024 to 2026
$737k
NICHD NIH HHS R00 HD105001NICHD NIH HHS R01 HD100035NICHD NIH HHS R01 HD119238NIGMS NIH HHS R35 GM122580
6 · The paper itself

Abstract

Embryonic cell differentiation depends on reprogramming of the oocyte and sperm nucleus into a transient totipotent state. In zebrafish, this coincides with genome activation, which is regulated by the pioneer factors Nanog, Pou5f3, and Sox19b (NPS). Here, we investigate the role of NPS in developmental reprogramming and differentiation by analyzing the fate of NPS mutant cells in a wild-type embryo using single-cell RNA-seq. We find that many cells fail to activate transcription or undergo cell death, while others acquire gene expression profiles that resemble germ cells, neural progenitors, and motoneuron states. These cells achieve intermediate transcriptional states, revealing the essential role of NPS in coordinating nuclear and cytoplasmic reprogramming and preventing the premature activation of lineage-specific differentiation programs. These results demonstrate that most developmental programs require developmental reprogramming by NPS, yet some cells can bypass transient totipotency to achieve intermediate developmental states resembling wild-type states in vivo.

Indexed as

Cell DifferentiationCellular ReprogrammingZebrafishZebrafish ProteinsAnimalsEmbryo, NonmammalianGene Expression Regulation, DevelopmentalNanog Homeobox ProteinOctamer Transcription Factor-3Nanog Homeobox ProteinOctamer Transcription Factor-3Pou5f3 protein, zebrafishZebrafish Proteinscell identitycell statesCP: Developmental biologydevelopmentdifferentiationpluripotency factorsreprogrammingsingle-cell transcriptomics

Identifiers

PMID41171758
PMCPMC12841453

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LicenceCC BY-NC
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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.