# Single cell analysis of the human pancreas in type 1 diabetes

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $782,901

## Abstract

PROJECT SUMMARY/ABSTRACT
Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing beta cells in pancreatic
islets. In T1D the interplay between immune, endothelial, and endocrine cells in the islet niche leads to beta cell
dysfunction and/or destruction; however, there is limited knowledge of the molecular blueprint that initiates and
drives immune-mediated beta cell destruction. Recent single cell RNA-seq (scRNA-seq) profiling studies of
human pancreas and islets from non-diabetic donors lack the resolution to characterize immune cells.
Furthermore, T1D-related changes in the islet cell repertoire have not been comprehensively analyzed, and cell
type-resolved epigenomic maps of gene regulatory elements remain to be generated for T1D-relevant cell types.
When intersected with genetic variants from genome-wide T1D association studies, such maps could help
pinpoint cells and genes with causal roles in T1D. To fill these knowledge gaps, we have assembled a team of
highly accomplished researchers in islet biology and diabetes (Sander), genetics and genomics of diabetes
(Gaulton) and functional genomics (Ren, UCSD Center for Epigenomics). The proposed project will apply novel
single nuclei (sn) technologies to characterize the epigenomic (Aim 1) and transcriptomic (Aim 2) profiles of
individual T1D-relevant cells in the pancreas of non-diabetic and T1D individuals. To enrich cell types most
relevant for T1D pathogenesis (i.e. endocrine, immune and endothelial cells), we will deplete acinar cells from
whole pancreas preparations. From these enriched cell preparations, we will generate maps of accessible
chromatin (snATAC-seq) and gene expression (snRNA-seq). First, we will generate reference maps using fresh
pancreatic tissue from non-diabetic donors, and then employ our recent adaptions of snATAC-seq and snRNA-
seq technology to profile frozen, archived pancreata from non-diabetic, T1D antibody-positive, and T1D donors
in the Network for Pancreatic Organ Donors with Diabetes (nPOD) biorepository. In Aim 3, we will integrate
snATAC-seq and snRNA-seq data generated in Aims 1 and 2 with T1D genetic association data to identify
pancreatic cell types and regulatory programs involved in T1D pathogenesis. This analysis will 1) define cell
types and subtypes and their regulatory programs in the non-diabetic pancreas, 2) identify T1D-dependent
changes in the existence, composition, regulation and inter-connectivity of pancreatic cell types, and 3) identify
cells, networks and genes with likely causal roles in T1D by integrating snATAC-seq and snRNA-seq with T1D
genetic association data. By generating reference maps of chromatin and gene expression in pancreatic cells
from non-diabetic and T1D individuals, this proposal will identify resident immune and other cells that arise and
change during T1D that can serve as novel biomarkers of disease and which will inform strategies for early
intervention. Further integration with genetic d...

## Key facts

- **NIH application ID:** 10009390
- **Project number:** 5U01DK120429-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Kyle Jeffrie Gaulton
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $782,901
- **Award type:** 5
- **Project period:** 2018-09-25 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009390

## Citation

> US National Institutes of Health, RePORTER application 10009390, Single cell analysis of the human pancreas in type 1 diabetes (5U01DK120429-03). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10009390. Licensed CC0.

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