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首页> 外文期刊>Cell stem cell >Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+Intestinal Stem Cells
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Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+Intestinal Stem Cells

机译：分泌物前体的分泌前体中的染色质可访问性的动态重组，LGR5 +肠干细胞

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摘要

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.
机译：复制LGR5（+）干细胞和静态BMI1（+）细胞在体内表现为肠干细胞（ISC）。破坏LGR5（+）ISCs从分泌或吸收祖细胞和Paneth细胞前体的中皮更新从BMI1（+）细胞，揭示肠土隐窝内的高度可塑性。在这里，我们表明来自BMI1 GFP小鼠的GFP（+）细胞是预先肠癌细胞，并且我们将CD69（+）CD274（+）细胞鉴定为相关脚卵细胞前体。在丢失本机LGR5（+）ISC时，两个人群恢复LGR5（+）细胞标识。虽然活性组蛋白标记类似地分布在LGR5（+）ISC和两种主要谱系的祖细胞之间，但是在分泌细胞中选择性地打开血管限制基因表达的数千个顺式元素。此辅助功能签名在Crypt再生期间动态转换为LGR5（+）ISCS的。除了建立BMI1（GFP +）细胞的性质之外，这些发现揭示了染色质地如何下潜肠道细胞多样性和消化剂来恢复ISC功能和肠道稳态​​。

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