Evidence map›Paper›PMID 41093834›Full record

ArticleNature communications2025

Genome-wide CRISPR Screen Identifies Sec31A as a Key Regulator of Alpha Cell Survival.

Kimitaka Shibue, Sevim Kahraman, Jorge Ivan Castillo-Quan, Dario F De Jesus, Jiang Hu, Hiroyuki Morita, T Keith Blackwell, Peng Yi, Rohit N Kulkarni

Abstract read
In one paragraph

Article in Nature communications, 2025. 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. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Kimitaka ShibueIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
Sevim KahramanIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2880-6589
Jorge Ivan Castillo-QuanIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6324-2854
Dario F De JesusIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
Jiang HuIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
Hiroyuki MoritaMedical Research Institute, KITANO HOSPITAL, Osaka, Japan.
T Keith BlackwellIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3763-9134
Peng YiIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7830-4694
Rohit N KulkarniIslet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA. Rohit.Kulkarni@joslin.harvard.edu.ORCID http://orcid.org/0000-0001-5029-6119

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Signaling mechanisms that detect stress and maintain homeostasis - Research Supplement to Promote Diversity in Health-Related ResearchR35GM122610 · NIGMS · JOSLIN DIABETES CENTER · PI KAHN, C RONALD · 2017 to 2025
$4.7M
Uncovering Conserved Lipid Homeostasis Mechanisms that Mediate Longevity after Germ Cell Loss in C. ElegansR01AG054215 · NIA · JOSLIN DIABETES CENTER · PI JEAN E. SCHAFFER · 2017 to 2026
$3.9M
Interrogating the role of m6A mRNA methylation in the aging of the β-cell and diabetesR00DK135927 · NIDDK · UNIVERSITY OF CHICAGO · PI Dario F De Jesus · 2025 to 2026
$498k
Interrogating the role of m6A mRNA methylation in the aging of the β-cell and diabetesK99DK135927 · NIDDK · JOSLIN DIABETES CENTER · PI F DE JESUS, DARIO · 2023 to 2024
$180k
MEXT | Japan Society for the Promotion of Science (JSPS) JP22K16404NIA NIH HHS R01 AG054215NIDDK NIH HHS K99 DK135927NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R00 DK135927U.S. Department of Health & Human Services | National Institutes of Health (NIH) DK067536U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AG054215U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35GM122610
6 · The paper itself

Abstract

Glucagon, secreted by pancreatic alpha cells, is essential for maintaining normal blood glucose levels. In type 1 and advanced type 2 diabetes, alpha cells often fail to respond to low glucose, yet the mechanisms underlying  their stress resistance remain unclear. To investigate this, we performed a genome-wide CRISPR screen and identify Sec31A, a gene involved in transporting proteins from the endoplasmic reticulum (ER), as a key regulator of alpha cell survival under stress. We show that loss of Sec31A enhances survival in stressed mouse alpha cells and in C. elegans. In human islets, SEC31A expression increases in alpha cells under inflammatory stress, and this upregulation is reversed by reducing ER stress. Functional studies in lab-grown human islet clusters reveal distinct responses in alpha versus beta cells following Sec31A suppression. We also find that Sec31A interacts with the insulin receptor, suggesting a link between stress adaptation and insulin signaling in alpha cells.

Indexed as

Glucagon-Secreting CellsVesicular Transport ProteinsAnimalsCaenorhabditis elegansCell SurvivalClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsEndoplasmic ReticulumEndoplasmic Reticulum StressGlucagonHumansInsulinInsulin-Secreting CellsMiceReceptor, InsulinSignal TransductionGlucagonInsulinReceptor, InsulinVesicular Transport Proteins

Identifiers

PMID41093834
PMCPMC12528718

What OpenQuestion holds

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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.