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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 Bmi1GFP 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 Bmi1GFP+ cells, these findings reveal how chromatin status underlies intestinal cell diversity and dedifferentiation to restore ISC function and intestinal homeostasis.
Pubmed ID: 28648363 RIS Download
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THIS RESOURCE IS NO LONGER IN SERVICE. Documented on September 23,2022. Consortium to advance the understanding of intestinal epithelial stem cell biology during development, homeostasis, regeneration and disease. Its immediate goals are to isolate, characterize, culture and validate populations of intestinal stem cells; answer major questions in stem cell biology of the intestinal epithelium; and accelerate research by making information and resources available to the research community. Resources include data sets, protocols, and a resource catalog. Long-term goals include: 1) laying the ground work for therapeutic manipulation of the intestinal epithelium 2) contributing to the greater understanding of stem cell biology through knowledge of the intestine as a model stem cell-driven system. Research Projects are housed at 8 institutions across the nation: Oregon Health & Science University, Stanford University, Stowers Institute for Medical Research, University of California, Los Angeles School of Medicine (UCLA) (partnered with the VA Greater Los Angeles), University of North Carolina, Chapel Hill (UNC), University of Oklahoma, University of Pennsylvania, and University of Pittsburgh.
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Mus musculus with name BKa.Cg-Ptprcb Bmi1
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