Epigenetic and Transcriptional Dynamics of Notch Program in Intestinal Differentiation

The equilibrium between stem cell self-renewal and differentiation followed by proper lineage specification of progenitor cells is considered imperative for maintaining intestinal homeostasis. In the hierarchical model, intestinal differentiation is defined by the stepwise acquisition of lineage-specific mature cell features, where Notch signaling and lateral inhibition instructively regulate the cell-fate decisions. Recent studies reveal a broadly permissive intestinal chromatin underlies the lineage plasticity and adaptation to diet mediated by Notch transcriptional program. Here, we review the conventional understanding of Notch programming in intestinal differentiation and describe how new data from epigenetic and transcriptional analyses may refine or revise the current view. We provide instructions on sample preparation and data analysis and explain how to use ChIP-seq and scRNA-seq in combination of lineage tracing assay to determine the dynamics of Notch program and intestinal differentiation in the context of dietary and metabolic regulation of cell-fate decisions.