Evidence map›Paper›PMID 40027657›Full record

ArticlebioRxiv : the preprint server for biology2025

Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs driving type 1 diabetes progression.

Rebecca Melton, Sara Jimenez, Weston Elison, Luca Tucciarone, Abigail Howell, Gaowei Wang, Denise Berti, Elisha Beebe, Michael Miller, Chun Zeng and 13 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Rebecca MeltonBiomedical sciences program, University of California San Diego, La Jolla CA.
Sara JimenezDepartment of Computational Health, Institute of Computational Biology, Helmholtz, Munich, Germany.
Weston ElisonBiomedical sciences program, University of California San Diego, La Jolla CA.
Luca TucciaroneDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Abigail HowellDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Gaowei WangDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Denise BertiDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Elisha BeebeDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Michael MillerCenter for Epigenomics, University of California San Diego, La Jolla CA.
Chun ZengDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Carolyn McGrailBiomedical sciences program, University of California San Diego, La Jolla CA.
Kennedy VanderStelDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Katha KorgaonkarDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Ruth ElgamalBiomedical sciences program, University of California San Diego, La Jolla CA.
Hannah MummeyBioinformatics and systems biology program, University of California San Diego, La Jolla CA.
Joshua ChiouPfizer Research and Discovery, Pfizer Inc, Cambridge, MA.
Emily GriffinDepartment of Pediatrics, University of California San Diego, La Jolla CA.
Irina KusmartsevaDepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville FL.
Mark AtkinsonDepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville FL.
Sebastian PreisslCenter for Epigenomics, University of California San Diego, La Jolla CA.
Fabian J TheisDepartment of Computational Health, Institute of Computational Biology, Helmholtz, Munich, Germany.
Maike SanderDepartment of Pediatrics, University of California San Diego, La Jolla CA.ORCID 0000-0001-5308-7785
Kyle J GaultonDepartment of Pediatrics, University of California San Diego, La Jolla CA.

Funding

Project 3P01AI042288 · NIAID · UNIVERSITY OF FLORIDA · PI Todd Michael Brusko · 1997 to 2026
$32.9M
The Human Pancreas Analysis Program for Type 2 DiabetesU01DK123594 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Robert Babak Faryabi, KLAUS H KAESTNER · 2019 to 2026
$25.0M
Penn integrated Human Pancreas procurement and Analysis ProgramUC4DK112217 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BETTS, MICHAEL R, FELDMAN, MICHAEL D · 2016 to 2020
$17.8M
Supplement to Integrated Program for Human Pancreas Procurement and AnalysisUC4DK112232 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., POWERS, ALVIN C · 2016 to 2020
$8.4M
Human Pancreas Analysis Program-T2DU01DK123716 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., BOTTINO, RITA · 2019 to 2024
$6.6M
Genetic mechanisms of type 1 diabetes risk in stress-induced pancreatic isletsR01DK122607 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAULTON, KYLE JEFFRIE · 2019 to 2022
$4.4M
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
NIAID NIH HHS P01 AI042288NIDDK NIH HHS R01 DK122607NIDDK NIH HHS U01 DK120429NIDDK NIH HHS U01 DK123594NIDDK NIH HHS U01 DK123716NIDDK NIH HHS UC4 DK112217NIDDK NIH HHS UC4 DK112232
6 · The paper itself

Abstract

Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here we performed single nucleus multiomics and spatial transcriptomics in up to 32 non-diabetic (ND), autoantibody-positive (AAB+), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine sub-types. Beta, acinar, and other cell types, and related cellular niches, had altered abundance and gene activity in T1D progression, including distinct pathways altered in AAB+ compared to T1D. We identified epigenomic drivers of gene activity in T1D and AAB+ which, combined with genetic association, revealed causal pathways of T1D risk including antigen presentation in beta cells. Finally, single cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting beta cell regulation. Overall, these results revealed drivers of T1D progression in the pancreas, which form the basis for therapeutic targets for disease prevention.

Identifiers

PMID40027657
PMCPMC11870426

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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.