Journal
CELL STEM CELL
Volume 21, Issue 1, Pages 65-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2017.05.001
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Funding
- Intestinal Stem Cell Consortium of the NIDDK [U01DK103152]
- NIAID
- NIH [R01DK081113, F32DK103453, P50CA127003]
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Replicating Lgr5(+) stem cells and quiescent Bmi1(+) cells behave as intestinal stem cells (ISCs) in vivo. Disrupting Lgr5(+) ISCs triggers epithelial renewal from Bmi1(+) cells, from secretory or absorptive progenitors, and from Paneth cell precursors, revealing a high degree of plasticity within intestinal crypts. Here, we show that GFP(+) cells from Bmi1 GFP mice are preterminal enteroendocrine cells and we identify CD69(+) CD274(+) cells as related goblet cell precursors. Upon loss of native Lgr5(+) ISCs, both populations revert toward an Lgr5(+) cell identity. While active histone marks are distributed similarly between Lgr5(+) ISCs and progenitors of both major lineages, thousands of cis elements that control expression of lineage-restricted genes are selectively open in secretory cells. This accessibility signature dynamically converts to that of Lgr5(+) ISCs during crypt regeneration. Beyond establishing the nature of Bmi1(GFP+) cells, these findings reveal how chromatin status underlies intestinal cell diversity and dedifferentiation to restore ISC function and intestinal homeostasis.
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