Evidence map›Paper›PMID 38395976›Full record

ArticleNature communications2024

Complex regulatory networks influence pluripotent cell state transitions in human iPSCs.

Timothy D Arthur, Jennifer P Nguyen, Agnieszka D'Antonio-Chronowska, Hiroko Matsui, Nayara S Silva, Isaac N Joshua, iPSCORE Consortium, André D Luchessi, William W Young Greenwald, Matteo D'Antonio and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
5.6field-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

19 citing papers in PubMed, 24 citations in OpenAlex.

  1. Inferring Gene Regulatory Networks in Stem Cells: Methods and Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. Article
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  6. Distinguishing causal from tagging enhancers using single-cell multiome data.medRxiv : the preprint server for health sciences · 2026
    Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Epigenetic networks coordinate DNA methylation across the genome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  12. Pluripotent cell states and fates in human embryo models.Development (Cambridge, England) · 2025
    Review
  13. Article
  14. Article
  15. Pluripotency genes of mammals: a network at work.Frontiers in bioengineering and biotechnology · 2025
    Review
  16. UBR-5 and UBE2D mediate timely exit from stem fate via destabilization of poly(A)-binding protein PABP-2 in cell state transition.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Article
  18. Article
  19. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Timothy D ArthurBiomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, 92093, USA.
Jennifer P NguyenDivision of Biomedical Informatics, University of California, San Diego, La Jolla, CA, 92093, USA.
Agnieszka D'Antonio-ChronowskaDepartment of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA.
Hiroko MatsuiInstitute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
Nayara S SilvaNortheast Biotechnology Network (RENORBIO), Graduate Program in Biotechnology, Federal University of Rio Grande do Norte, Natal, Brazil.
Isaac N JoshuaInstitute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
iPSCORE Consortium
André D LuchessiNortheast Biotechnology Network (RENORBIO), Graduate Program in Biotechnology, Federal University of Rio Grande do Norte, Natal, Brazil.
William W Young GreenwaldBioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, 92093, USA.
Matteo D'AntonioDivision of Biomedical Informatics, University of California, San Diego, La Jolla, CA, 92093, USA.
Martin F PeraThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.ORCID 0000-0001-6239-0428
Kelly A FrazerDepartment of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA. kafrazer@health.ucsd.edu.ORCID 0000-0002-6060-8902
University of California San Diego · USSalk Institute for Biological Studies · USUniversidade Federal do Rio Grande do Norte · BRJackson Laboratory · US

Funding

Genetic & Social Determinants of Health: Center for Admixture Science and TechnologyRM1HG011558 · NHGRI · YALE UNIVERSITY · PI FRAZER, KELLY A, GYMREK, MELISSA · 2021 to 2025
$11.2M
REGULATORY GENOMIC STUDIES IN A COHORT OF IPS CELL DERIVED CARDIOMYOCYTESU01HL107442 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EVANS, SYLVIA M, FRAZER, KELLY A · 2011 to 2016
$9.8M
San Diego Biomedical Informatics Education & Research (SABER)T15LM011271 · NLM · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHAMIM NEMATI · 2012 to 2026
$9.7M
Commercialization of HaploSeq as a Service (HaaS) for generating chromosome-span phased genome and exome sequence informationR44HG008118 · NHGRI · ARIMA GENOMICS, INC. · PI DIXON, JESSE R, LAURENT, LOUISE CHANG · 2018 to 2019
$1.7M
Optimizing HaploSeq for whole-genome phased haplotypes in biomedical applicationsR41HG008118 · NHGRI · ARIMA GENOMICS, LLC · PI FRAZER, KELLY A, HEINTZMAN, NATE · 2015 to 2016
$822k
Pancreas cell type-specific regulatory variants and T2D disease risk associationF31DK131867 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NGUYEN, JENNIFER PHUONG · 2022 to 2023
$80k
Cardiac stage-specific regulatory variants and their disease risk associationF31HL158198 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ARTHUR, TIMOTHY DONALD · 2021 to 2022
$79k
NHGRI NIH HHS R41 HG008118NHGRI NIH HHS R44 HG008118NHGRI NIH HHS RM1 HG011558NHLBI NIH HHS F31 HL158198NHLBI NIH HHS U01 HL107442NIDDK NIH HHS F31 DK131867NLM NIH HHS T15 LM011271
6 · The paper itself

Abstract

Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Analyzing hundreds of hiPSCs derived from different individuals, we show the proportions of these pluripotent states vary considerably across lines. We discover 13 gene network modules (GNMs) and 13 regulatory network modules (RNMs), which are highly correlated with each other suggesting that the coordinated co-accessibility of regulatory elements in the RNMs likely underlie the coordinated expression of genes in the GNMs. Epigenetic analyses reveal that regulatory networks underlying self-renewal and pluripotency are more complex than previously realized. Genetic analyses identify thousands of regulatory variants that overlapped predicted transcription factor binding sites and are associated with chromatin accessibility in the hiPSCs. We show that the master regulator of pluripotency, the NANOG-OCT4 Complex, and its associated network are significantly enriched for regulatory variants with large effects, suggesting that they play a role in the varying cellular proportions of pluripotency states between hiPSCs. Our work bins tens of thousands of regulatory elements in hiPSCs into discrete regulatory networks, shows that pluripotency and self-renewal processes have a surprising level of regulatory complexity, and suggests that genetic factors may contribute to cell state transitions in human iPSC lines.

Indexed as

Induced Pluripotent Stem CellsCell DifferentiationChromatinGene Regulatory NetworksHumansOctamer Transcription Factor-3ChromatinOctamer Transcription Factor-3

Identifiers

PMID38395976
PMCPMC10891157
OpenAlexW4392111117

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.