Single-cell transcriptomic gene regulatory network analysis uncovers the alteration of colonic stem and immune cell homeostasis in Nr4a1 knockout mice

However, its role in regulating intestinal crypt homeostasis remains unclear. To assess the effects of NR4A on intestinal epithelial, stromal and immune cell heterogeneity and functional phenotypes, we utilized single-cell transcriptomics and advanced analytic strategies to generate a high-quality atlas for the colonic epithelium from wild-type and whole body Nr4a1 knockout mice.

Here we observed a widespread effect of Nr4a1 deletion on intercellular communication involving intestinal stem cells, macrophages, T and B cells, and fibroblasts, indicating a complex and pervasive remodeling of the colonic epithelial and immune microenvironments and their regulatory networks. This alteration in cell-cell crosstalk was associated with an elevated single-cell entropy, indicative of higher differentiation potential and stem-like properties in epithelial, stromal and immune cell types.