Chromatin analysis of adult pluripotent stem cells reveals a unique stemness maintenance strategy.

Chromatin analysis of adult pluripotent stem cells reveals a unique stemness maintenance strategy.
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DOI:
10.1126/sciadv.adh4887
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发表时间:
2023-10-06
期刊:
影响因子:
13.6
通讯作者:
van Wolfswinkel, Josien C.
van Wolfswinkel, Josien C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Poulet, Axel;Kratkiewicz, Arcadia J.;Li, Danyan;van Wolfswinkel, Josien C.

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许多高度再生的生物体在其一生中保持成体多能干细胞,但如何实现多能性的长期维持尚不清楚。为了解读成体多能干细胞的调控逻辑,我们分析了真涡虫Schmidtea medialacea干细胞基因的染色质组织。我们确定了一个特殊的染色质状态的干细胞基因,这是不同的组织特异性基因,类似于组成型基因。当组织特异性启动子具有可检测的转录因子结合位点时,干细胞特异性基因的启动子反而具有广泛降低核小体结合亲和力的序列特征。这种基因组织使多能性相关基因表达成为这些细胞中的默认状态,这是由干细胞中染色质重塑剂ISWI和SNF2的活性维持的。成体多能细胞通过染色质重塑来调节基因表达,而不依赖于特定的转录因子。
Many highly regenerative organisms maintain adult pluripotent stem cells throughout their life, but how the long-term maintenance of pluripotency is accomplished is unclear. To decipher the regulatory logic of adult pluripotent stem cells, we analyzed the chromatin organization of stem cell genes in the planarian Schmidtea mediterranea. We identify a special chromatin state of stem cell genes, which is distinct from that of tissue-specific genes and resembles constitutive genes. Where tissue-specific promoters have detectable transcription factor binding sites, the promoters of stem cell–specific genes instead have sequence features that broadly decrease nucleosome binding affinity. This genic organization makes pluripotency-related gene expression the default state in these cells, which is maintained by the activity of chromatin remodelers ISWI and SNF2 in the stem cells. Adult pluripotent cells regulate gene expression through chromatin remodelers, without relying on specific transcription factors.
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