Evidence map›Paper›PMID 41927580›Full record

ArticleNature communications2026

Depolymerizing F-actin accelerates the exit from pluripotency to enhance stem cell-derived islet differentiation.

Nathaniel J Hogrebe, Mason D Schmidt, Punn Augsornworawat, Sarah E Gale, Mira Shunkarova, Jeffrey R Millman

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. ProtectiveiScience · 2026
    Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Nathaniel J HogrebeDivision of Endocrinology, Metabolism and Lipid Research Washington University School of Medicine MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-6282-2056
Mason D SchmidtDivision of Endocrinology, Metabolism and Lipid Research Washington University School of Medicine MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1303-9911
Punn AugsornworawatDepartment of Immunology Faculty of Medicine Siriraj Hospital Mahidol University, Bangkok, Thailand.ORCID http://orcid.org/0000-0001-8602-5433
Sarah E GaleDivision of Endocrinology, Metabolism and Lipid Research Washington University School of Medicine MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, USA.
Mira ShunkarovaDivision of Endocrinology, Metabolism and Lipid Research Washington University School of Medicine MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, USA.
Jeffrey R MillmanDivision of Endocrinology, Metabolism and Lipid Research Washington University School of Medicine MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, USA. jmillman@wustl.edu.ORCID http://orcid.org/0000-0003-0426-3492

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Irfan J Lodhi · 2013 to 2026
$27.1M
STUDYING THE ROLE OF THE MICROENVIRONMENT ON DIFFERENTIATION AND MATURATION OF BETA CELLSR01DK114233 · NIDDK · WASHINGTON UNIVERSITY · PI Jeffrey Robert Millman · 2017 to 2026
$3.6M
Cytoskeletal regulation of gut tube organogenesis and subsequent maturation of stem cell-derived isletsK01DK144664 · NIDDK · WASHINGTON UNIVERSITY · PI Nathaniel James Hogrebe · 2025 to 2026
$278k
JDRF 3-SRA-2024-1555-S-BNIDDK NIH HHS K01 DK144664NIDDK NIH HHS P30 DK020579U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK114233
6 · The paper itself

Abstract

In this study, we demonstrate that cytoskeletal state at the onset of directed differentiation impacts the exit of human pluripotent stem cells (hPSCs) from pluripotency and downstream lineage specification. In particular, depolymerizing F-actin with latrunculin A (latA) during the first 24 h of definitive endoderm formation facilitates efficient loss of pluripotency and alters Activin/Nodal, BMP, c-Jun, and WNT signaling dynamics. These signaling changes influence downstream patterning of the gut tube, leading to improved pancreatic progenitor identity and decreased expression of markers associated with other endodermal lineages. Continued differentiation generates islets containing a higher percentage of β cells that exhibit improved maturation, insulin secretion, and ability to reverse hyperglycemia. Furthermore, this latA treatment reduces enterochromaffin cells in the final cell population and corrects differentiations from hPSC lines that otherwise fail to consistently produce pancreatic islets, highlighting the importance of cytoskeletal signaling at the onset of directed differentiation.

Indexed as

ActinsCell DifferentiationIslets of LangerhansPluripotent Stem CellsAnimalsBridged Bicyclo Compounds, HeterocyclicCell LineEndodermHumansInsulinSignal TransductionThiazolidinesActinsBridged Bicyclo Compounds, HeterocyclicInsulinlatrunculin AThiazolidines

Identifiers

PMID41927580
PMCPMC13219671

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.