Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs

A number of studies have reported cell heterogeneity within the developing mouse pancreas, as well as the transcriptional profiles corresponding to various cell states. The upstream mechanisms that initiate and maintain gene expression programs across cell states, however, remain largely unknown. Here, we applied single-nucleus ATAC-Seq to developing mouse pancreas to generate an atlas of chromatin accessibility, at single-cell resolution. Our goals were first, to generate an atlas of chromatin accessibility of embryonic mouse pancreas, at single-cell resolution, that can serve as a resource for the field. We aimed to provide such a resource not only for epithelial cells within the pancreas, but for non-epithelial (e.g., mesenchymal) as well. Our second goal was to identify gene regulatory networks governing cell fate transitions through integration of single-cell chromatin accessibility and gene expression data. Overall design: To investigate chromatin accessibility of the developing pancreas, we performed snATAC-Seq on E14.5 and E17.5 murine pancreas from eFev-YFP mice using the 10x Genomics scATAC Seq platform. We profiled both whole pancreas, as well as eFev-YFP+ sorted cells, the latter designed to enriched for endocrine progenitor cells.