Evidence map›Paper›PMID 37040771›Full record

ArticleDevelopmental cell2023

Understanding cell fate acquisition in stem-cell-derived pancreatic islets using single-cell multiome-inferred regulomes.

Han Zhu, Gaowei Wang, Kim-Vy Nguyen-Ngoc, Dongsu Kim, Michael Miller, Georgina Goss, Jenna Kovsky, Austin R Harrington, Diane C Saunders, Alexander L Hopkirk and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Developmental cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
29.8field-weighted citation impact, top 1% 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

50 citing papers in PubMed, 82 citations in OpenAlex.

  1. ProtectiveiScience · 2026
    Article
  2. Review
  3. Review
  4. Charting Endocrine Progenitors Across Species and Organs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. ProtectivebioRxiv : the preprint server for biology · 2025
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Han ZhuDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA.
Gaowei WangDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA.
Kim-Vy Nguyen-NgocDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA.
Dongsu KimDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA.
Michael MillerCenter for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Georgina GossCentre for Gene Therapy and Regenerative Medicine, King's College London, London SE1 9RT, UK.
Jenna KovskyDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA.
Austin R HarringtonDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA.
Diane C SaundersDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-0475, USA.
Alexander L HopkirkDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-0475, USA.
Rebecca MeltonDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA.
Alvin C PowersDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-0475, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA; VA Tennessee Valley Healthcare System, Nashville, TN 37212-2637, USA.
Sebastian PreisslCenter for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Francesca M SpagnoliCentre for Gene Therapy and Regenerative Medicine, King's College London, London SE1 9RT, UK.
Kyle J GaultonDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
Maike SanderDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, USA; Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: maike.sander@mdc-berlin.de.
University of California San Diego · USKing's College London · GBVanderbilt University Medical Center · USVanderbilt University · US

Funding

Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4M
Nkx6 gene function in pancreas developmentR01DK068471 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI WORTHAM, MATTHEW · 2004 to 2024
$6.6M
Functional Analysis of T2D Associated Non-coding SNPsU01DK105541 · NIDDK · LUDWIG INSTITUTE FOR CANCER RES LTD · PI FRAZER, KELLY A, REN, BING · 2015 to 2019
$4.6M
Single cell analysis of the human pancreas in type 1 diabetesU01DK120429 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAULTON, KYLE JEFFRIE, SANDER, MAIKE · 2018 to 2021
$3.1M
A 3D vascularized islet biomimetic to model type 1 diabetesUH3DK122639 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HUGHES, CHRISTOPHER C. W., SANDER, MAIKE · 2021 to 2023
$3.0M
Genetic Regulation of Adiposity and Associated CVD RisksR01DK064391 · NIDDK · WRIGHT STATE UNIVERSITY · PI TOWNE, BRADFORD · 2003 to 2007
$2.7M
A 3D vascularized islet biomimetic to model type 1 diabetesUG3DK122639 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HUGHES, CHRISTOPHER C. W., SANDER, MAIKE · 2019 to 2020
$2.1M
NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK064391NIDDK NIH HHS R01 DK068471NIDDK NIH HHS U01 DK105541NIDDK NIH HHS U01 DK120429NIDDK NIH HHS UG3 DK122639NIDDK NIH HHS UH3 DK122639
6 · The paper itself

Abstract

Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem-cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and pancreas from childhood and adult donors for comparison. We delineate major cell types, define their regulomes, and describe spatiotemporal gene regulatory relationships between transcription factors. CDX2 emerged as a regulator of enterochromaffin-like cells, which we show resemble a transient, previously unrecognized, serotonin-producing pre-β cell population in fetal pancreas, arguing against a proposed non-pancreatic origin. Furthermore, we observe insufficient activation of signal-dependent transcriptional programs during in vitro β cell maturation and identify sex hormones as drivers of β cell proliferation in childhood. Altogether, our analysis provides a comprehensive understanding of cell fate acquisition in stem-cell-derived islets and a framework for manipulating cell identities and maturity.

Indexed as

Insulin-Secreting CellsIslets of LangerhansPluripotent Stem CellsAdultCell DifferentiationHumansPancreasATAC-seqCDX2developmentfetal pancreasgene regulatory networkhuman pluripotent stem cellsisletspancreasRNA-seqserotoninsignalssingle-cell genomicstranscription factorsβ cell

Identifiers

PMID37040771
PMCPMC10175223
OpenAlexW4363677402

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.