Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+ Intestinal Stem Cells.
Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+ Intestinal Stem Cells.
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DOI：
10.1016/j.stem.2017.05.001
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发表时间：
2017-07-06
期刊：
影响因子：
23.9
通讯作者：
Shivdasani RA
中科院分区：
文献类型：
--
作者：
Jadhav U;Saxena M;O'Neill NK;Saadatpour A;Yuan GC;Herbert Z;Murata K;Shivdasani RA
复制的Lgr 5+干细胞和静止的Bmi 1+细胞在体内表现为肠干细胞（ISC）。破坏Lgr5+ ISCs触发上皮更新Bmi1+细胞，分泌或吸收祖细胞，和潘氏细胞前体，揭示了高度的可塑性肠隐窝内。在这里，我们表明，GFP+细胞从Bmi1GFP小鼠是前终端肠内分泌细胞，并确定CD69+CD274+细胞作为相关的杯状细胞前体。在失去天然Lgr5+ ISC后，两个群体都恢复为Lgr5+细胞身份。虽然活性组蛋白标记在两个主要谱系的Lgr5+ ISC和祖细胞之间分布相似，但控制谱系限制基因表达的数千个顺式元件在分泌细胞中选择性开放。这个可访问性签名在crypt重新生成期间动态转换为Lgr5+ ISC的签名。除了确定Bmi1GFP+细胞的性质外，这些发现还揭示了染色质状态如何成为肠细胞多样性和去分化的基础，以恢复ISC功能和肠内稳态。
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 pre-terminal enteroendocrine cells and identify CD69+CD274+ cells as related goblet cell precursors. Upon loss of native Lgr5+ ISCs, both populations revert towards 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.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
23.9
作者：
Metcalfe, Ciara;Kljavin, Noelyn M.;de Sauvage, Frederic J.
通讯作者：
de Sauvage, Frederic J.
影响因子：
64.8
作者：
Buczacki, Simon J. A.;Zecchini, Heather Ireland;Winton, Douglas J.
通讯作者：
Winton, Douglas J.