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.

中文翻译：

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分泌前体去分化为 Lgr5+ 肠干细胞过程中染色质可及性特征的动态重组。

复制的 Lgr5 ⁺干细胞和静止的 Bmi1 ⁺细胞在体内表现为肠道干细胞 (ISC)。破坏 Lgr5 ⁺ ISC 会触发 Bmi1 ⁺细胞、分泌或吸收祖细胞以及潘氏细胞前体的上皮更新，揭示肠隐窝内的高度可塑性。在这里，我们表明来自 Bmi1 ^{GFP小鼠的 GFP +}细胞是前终末期肠内分泌细胞，我们将 CD69 ⁺ CD274 ⁺细胞鉴定为相关的杯状细胞前体。在失去原生 Lgr5 ⁺ ISC 后，两个种群都会恢复到 Lgr5 ⁺细胞身份。虽然活性组蛋白标记在 Lgr5 ⁺ ISC 和两个主要谱系的祖细胞之间的分布相似，但在分泌细胞中选择性地打开了数千个控制谱系限制基因表达的顺式元件。此可访问性签名在地穴再生期间动态转换为 Lgr5 ⁺ ISCs 的可访问性签名。^{除了确定 Bmi1 GFP+}细胞的性质外，这些发现还揭示了染色质状态如何成为肠道细胞多样性和去分化的基础，以恢复 ISC 功能和肠道稳态​​。