Evidence mapPaperPMID 36070683Full record

ArticleCell metabolism2022

3D chromatin maps of the human pancreas reveal lineage-specific regulatory architecture of T2D risk.

Chun Su, Long Gao, Catherine L May, James A Pippin, Keith Boehm, Michelle Lee, Chengyang Liu, Matthew C Pahl, Maria L Golson, Ali Naji and 4 more

Open access · greenAbstract read
In one paragraph

Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. Article
  3. Variant-to-gene mapping identifiesbioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Med14 phosphorylation shapes genomic response to GLP-1 agonists.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. DiabetesOmic: A comprehensive multi-omics diabetes database.Computational and structural biotechnology journal · 2025
    Article
  20. 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

14 authors at 2 institutions in 1 country.

Chun SuDivision of Human Genetics and Endocrinology & Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Long GaoInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Catherine L MayInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
James A PippinDivision of Human Genetics and Endocrinology & Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Keith BoehmDivision of Human Genetics and Endocrinology & Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Michelle LeeInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Chengyang LiuInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Matthew C PahlDivision of Human Genetics and Endocrinology & Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Maria L GolsonInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Ali NajiInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
HPAP ConsortiumThe Human Pancreas Analysis Program (RRID: SCR_016202).
Struan F A GrantDivision of Human Genetics and Endocrinology & Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: grants@chop.edu.
Andrew D WellsCenter for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: wellsa@chop.edu.
Klaus H KaestnerInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: kaestner@pennmedicine.upenn.edu.
University of Pennsylvania · USChildren's Hospital of Philadelphia · US

Funding

Univ of Pennsylvania Diabetes Endocrinology Res CTRP30DK019525 · UNIVERSITY OF PENNSYLVANIA · 1986 to 2025
$10.9M
Human Pancreas Analysis Program for Type 1 Diabetes - HPAP-T1DU01DK112217 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$9.0M
The Human Pancreas Analysis Program for Type 2 DiabetesU01DK123594 · NIDDK · UNIVERSITY OF PENNSYLVANIA · 2022 to 2025
$8.0M
Vanderbilt Diabetes Research CenterP30DK020593 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$1.8M
Human Pancreas Analysis Program-T2DU01DK123716 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARK A. ATKINSON, Rita Bottino · 2022 to 2022
$1.1M
NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK020593NIDDK NIH HHS U01 DK112217NIDDK NIH HHS U01 DK123594NIDDK NIH HHS U01 DK123716NIDDK NIH HHS UC4 DK112217NIDDK NIH HHS UM1 DK126194
6 · The paper itself

Abstract

Three-dimensional (3D) chromatin organization maps help dissect cell-type-specific gene regulatory programs. Furthermore, 3D chromatin maps contribute to elucidating the pathogenesis of complex genetic diseases by connecting distal regulatory regions and genetic risk variants to their respective target genes. To understand the cell-type-specific regulatory architecture of diabetes risk, we generated transcriptomic and 3D epigenomic profiles of human pancreatic acinar, alpha, and beta cells using single-cell RNA-seq, single-cell ATAC-seq, and high-resolution Hi-C of sorted cells. Comparisons of these profiles revealed differential A/B (open/closed) chromatin compartmentalization, chromatin looping, and transcriptional factor-mediated control of cell-type-specific gene regulatory programs. We identified a total of 4,750 putative causal-variant-to-target-gene pairs at 194 type 2 diabetes GWAS signals using pancreatic 3D chromatin maps. We found that the connections between candidate causal variants and their putative target effector genes are cell-type stratified and emphasize previously underappreciated roles for alpha and acinar cells in diabetes pathogenesis.

Indexed as

Diabetes Mellitus, Type 2Insulin-Secreting CellsIslets of LangerhansChromatinGene Expression RegulationHumansChromatin3D chromatin mapsacinar cellalpha cellbeta cellislets of Langerhanstype 2 diabetes

Identifiers

PMID36070683
PMCPMC9664375
OpenAlexW4294783762

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.