This repository contains code and references used to perform all analyses in our manuscript describing changes in cell types, gene expression and gene regulation in the pancreas of individuals with Cystic Fibrosis-Related Diabetes (CFRD).
In this study we performed single cell and spatial characterization of the pancreas in cystic fibrosis (CF) consisting of 2.04M cells from 23 non-disease or CF donors. Important findings include:
- Large changes in composition and localizations of cell types in the pancreas during CF.
- Extensive changes in beta cell gene and network activity including increased stress responses and evidence for compensatory secretion.
- Islets in CF preferentially localized near large adipose tissue and collagen structures, and both areas were linked to beta cell loss due to signaling from adipocytes, macrophages, stellate, and high-mucin ductal cells.
- Pro-inflammatory and pro-fibrotic cell types have increase activity in CF, which is driven by increase proximity and crosstalk between them in specific niches.
- Ductal cells may transition to a high-mucin sub-type during CF with increased surival in the pro-fibrotic environment.
- Interactive tools to explore the Multiome and CosMx data are available at cfrdgenomics.org.
- Raw data from the paired snRNA-seq and snATAC-seq assays will be available on GEO after publication.
- Raw data from the CosMx spatial transcriptomics will be available on BIA after publication.
- Processed data will be available via AWS after publication.
Please cite any use of or data or code using: Single cell and spatial characterization of the human pancreas reveals drivers of beta cell dysfunction in cystic fibrosis. Mummey et al (2025), bioRxiv