Evidence map›Paper›PMID 38266068›Full record

ArticleDiabetes2024

DNA Methylation-Based Assessment of Cell Composition in Human Pancreas and Islets.

Zeina Drawshy, Daniel Neiman, Ori Fridlich, Ayelet Peretz, Judith Magenheim, Andrea V Rozo, Nicolai M Doliba, Doris A Stoffers, Klaus H Kaestner, Desmond A Schatz and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.3field-weighted citation impact, top 14% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Integrating Omics into Functional Biomarkers of Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024
    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

18 authors at 4 institutions in 3 countries.

Zeina DrawshyDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.ORCID 0000-0002-8327-3615
Daniel NeimanDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ori FridlichDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ayelet PeretzDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Judith MagenheimDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Andrea V RozoHuman Pancreas Analysis Program, University of Pennsylvania, Philadelphia, PA.
Nicolai M DolibaHuman Pancreas Analysis Program, University of Pennsylvania, Philadelphia, PA.
Doris A StoffersHuman Pancreas Analysis Program, University of Pennsylvania, Philadelphia, PA.
Klaus H KaestnerHuman Pancreas Analysis Program, University of Pennsylvania, Philadelphia, PA.
Desmond A SchatzDepartment of Pediatrics, University of Florida, Gainesville, FL.
Clive WasserfallDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL.
Martha Campbell-ThompsonDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL.
James ShapiroSurgery Department, Faculty of Medicine and Dentistry, Li Ka Shing Centre for Research, Edmonton, Alberta, Canada.
Tommy KaplanDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ruth ShemerDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Benjamin GlaserDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.ORCID 0000-0003-4711-5000
Agnes KlochendlerDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Yuval DorDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.ORCID 0000-0003-2456-2289
University of Pennsylvania · USUniversity of Florida · USHebrew University of Jerusalem · ILUniversity of Alberta · CA

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Patrick Seale · 1986 to 2026
$48.3M
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
Survival and potential of insulin-deficient beta cells in type 1 diabetesU01DK135001 · NIDDK · UNIVERSITY OF FLORIDA · PI SCHATZ, DESMOND ARTHUR · 2022 to 2025
$2.8M
RNA editing in islet function and inflammationR01DK133442 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Yuval Dor, Erez Levanon · 2023 to 2026
$2.1M
NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK133442NIDDK NIH HHS U01 DK123594NIDDK NIH HHS U01 DK123716NIDDK NIH HHS U01 DK135001NIDDK NIH HHS UC4 DK112217NIDDK NIH HHS UC4 DK112232
6 · The paper itself

Abstract

Assessment of pancreas cell type composition is crucial to the understanding of the genesis of diabetes. Current approaches use immunodetection of protein markers, for example, insulin as a marker of β-cells. A major limitation of these methods is that protein content varies in physiological and pathological conditions, complicating the extrapolation to actual cell number. Here, we demonstrate the use of cell type-specific DNA methylation markers for determining the fraction of specific cell types in human islet and pancreas specimens. We identified genomic loci that are uniquely demethylated in specific pancreatic cell types and applied targeted PCR to assess the methylation status of these loci in tissue samples, enabling inference of cell type composition. In islet preparations, normalization of insulin secretion to β-cell DNA revealed similar β-cell function in pre-type 1 diabetes (T1D), T1D, and type 2 diabetes (T2D), which was significantly lower than in donors without diabetes. In histological pancreas specimens from recent-onset T1D, this assay showed β-cell fraction within the normal range, suggesting a significant contribution of β-cell dysfunction. In T2D pancreata, we observed increased α-cell fraction and normal β-cell fraction. Methylation-based analysis provides an accurate molecular alternative to immune detection of cell types in the human pancreas, with utility in the interpretation of insulin secretion assays and the assessment of pancreas cell composition in health and disease. ARTICLE HIGHLIGHTS:

Indexed as

Diabetes Mellitus, Type 1Diabetes Mellitus, Type 2Glucagon-Secreting CellsInsulin-Secreting CellsIslets of LangerhansDNA MethylationHumansInsulinPancreasInsulin

Identifiers

PMID38266068
PMCPMC10958580
OpenAlexW4391164005

What OpenQuestion holds

Textmetadata
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.