Evidence map›Paper›PMID 32094658›Full record

ArticleNature biotechnology2020

Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells.

Nathaniel J Hogrebe, Punn Augsornworawat, Kristina G Maxwell, Leonardo Velazco-Cruz, Jeffrey R Millman

Abstract read
In one paragraph

Article in Nature biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 230 papers.

0numbers the graph read from it
0cells of the map it votes in
230citing 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

230 citing papers in PubMed.

  1. ProtectiveiScience · 2026
    Article
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  18. Review
  19. Article
  20. Mechanistic Role of Disulfidptosis in Type 2 Diabetes Mellitus.Molecular nutrition & food research · 2026
    Review

170 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Nathaniel J HogrebeDivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-6282-2056
Punn AugsornworawatDivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-8602-5433
Kristina G MaxwellDivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-0869-1662
Leonardo Velazco-CruzDivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA.
Jeffrey R MillmanDivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA. jmillman@wustl.edu.ORCID http://orcid.org/0000-0003-0426-3492

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI AIMEE S JAMES · 2001 to 2026
$128.0M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
DIABETES &RELATED METABOLIC DISEASEST32DK007120 · NIDDK · WASHINGTON UNIVERSITY · PI MARCO COLONNA, Maria Sara Remedi · 1986 to 2026
$15.7M
MAXIMIZING STUDENT DIVERSITY IN THE BIOMEDICAL SCIENCES AT WASHINGTON UNIVERSITYR25GM103757 · NIGMS · WASHINGTON UNIVERSITY · PI SKEATH, JAMES BENJAMIN · 2013 to 2022
$4.5M
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
Imaging, Modeling and Engineering of Diabetic TissuesT32DK108742 · NIDDK · WASHINGTON UNIVERSITY · PI NICHOLS, COLIN G · 2016 to 2020
$1.4M
NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1 TR002345NCI NIH HHS P30 CA091842NIDDK NIH HHS P30 DK020579NIDDK NIH HHS R01 DK114233NIDDK NIH HHS T32 DK007120NIDDK NIH HHS T32 DK108742NIGMS NIH HHS R25 GM103757
6 · The paper itself

Abstract

Generation of pancreatic β cells from human pluripotent stem cells (hPSCs) holds promise as a cell replacement therapy for diabetes. In this study, we establish a link between the state of the actin cytoskeleton and the expression of pancreatic transcription factors that drive pancreatic lineage specification. Bulk and single-cell RNA sequencing demonstrated that different degrees of actin polymerization biased cells toward various endodermal lineages and that conditions favoring a polymerized cytoskeleton strongly inhibited neurogenin 3-induced endocrine differentiation. Using latrunculin A to depolymerize the cytoskeleton during endocrine induction, we developed a two-dimensional differentiation protocol for generating human pluripotent stem-cell-derived β (SC-β) cells with improved in vitro and in vivo function. SC-β cells differentiated from four hPSC lines exhibited first- and second-phase dynamic glucose-stimulated insulin secretion. Transplantation of islet-sized aggregates of these cells rapidly reversed severe preexisting diabetes in mice at a rate close to that of human islets and maintained normoglycemia for at least 9 months.

Indexed as

ActinsAnimalsBasic Helix-Loop-Helix ProteinsBridged Bicyclo Compounds, HeterocyclicCell- and Tissue-Based TherapyCell DifferentiationCell EngineeringCell LineageCells, CulturedCytoskeletonDiabetes MellitusEndodermHomeodomain ProteinsHumansInsulin-Secreting CellsMiceActinsBasic Helix-Loop-Helix ProteinsBridged Bicyclo Compounds, HeterocyclicHomeodomain Proteinslatrunculin ANerve Tissue ProteinsNEUROG3 protein, humanpancreatic and duodenal homeobox 1 proteinThiazolidinesTrans-ActivatorsTubulin Modulators

Identifiers

PMID32094658
PMCPMC7274216

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.