GSE168373
Dynamic regulation of chromatin accessibility and transcription factors underlies distinct organ identity and function
After gut tube closure, different regional domains develop into uniquely functional organs. Our single cell analysis demonstrates that chromatin accessibility predicts lineage fate decisions, reflecting the transcriptional profiles of individual cells. Combining with bulk analyses, we have generated a comprehensive map of epigenetic changes over developmental time, revealing how chromatin accessibility and transcription factor (TF) binding cooperate to control organ identity and differentiation. Loss of the foregut and hindgut lineage-specific TFs, Sox2 and Cdx2, leads to the acquisition of accessibility profiles similar to neighbouring organs, while Sox2 overexpression in early development induces a loss of intestinal identity and pancreatic transformation into foregut fate precursors. Moreover, ectopic expression of Sox2 in normal adult and cancer intestinal and pancreatic tissues leads to lineage alterations, demonstrating its critical role in homeostasis and cancer. Together, these studies define the chromatin and transcriptional mechanisms of organ identity and lineage plasticity in development and disease. Overall design: We profiled genome-wide chromatin accessibility profile in single cell resolution (scATAC from 10x genomics) in mouse gut endoderm at E9.5. Bulk ATAC-seq and RNA-seq were also generated in mouse gut endoderm at E13.5. Each dataset has two replicates.