PRC2 Preserves Intestinal Progenitors and Restricts Secretory Lineage Commitment

The study concluded that Polycomb Repressive Complex 2 (PRC2) was essential for maintaining intestinal progenitor cells and limiting their differentiation into secretory lineages, thereby preserving the balance between different cell types in the intestine. PRC2 achieved this through H3K27 trimethylation, which regulated transcription factors like ATOH1 and GFI1. Loss of PRC2 activity led to increased goblet and enteroendocrine cells, reduced proliferating transit-amplifying cells, and impaired intestinal regeneration post-irradiation. These findings underscored PRC2's critical role in intestinal homeostasis, cell plasticity, and lineage choices, with potential implications for understanding intestinal diseases and developing targeted therapies.