PIWI-mediated control of tissue-specific transposons is essential for somatic cell differentiation.

PIWI-mediated control of tissue-specific transposons is essential for somatic cell differentiation.
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DOI:
10.1016/j.celrep.2021.109776
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发表时间:
2021-10-05
期刊:
影响因子:
8.8
通讯作者:
van Wolfswinkel JC
van Wolfswinkel JC
中科院分区:
生物学1区
文献类型:
--
作者:
Li D;Taylor DH;van Wolfswinkel JC

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Piwi蛋白是已知的动物种系中转座子沉默的介体,但也存在于高度再生动物的成年多能干细胞中,在那里它们是再生所必需的。对脊椎动物体细胞系统中核PIWI蛋白SMEDWI-2的研究揭示了转座子和细胞分化之间复杂的相互作用,其中转座子的一个子集在细胞分化过程中不可避免地被激活,需要PIWI蛋白来重新控制。SMEDWI-2的缺失导致与细胞类型特异性染色质重塑事件相关的组织特异性转座子去抑制,此外还导致谱系特异性基因的可获得性降低和细胞分化缺陷,从而导致致命的组织功能障碍。最后,我们证明了额外的PIWI蛋白在脊椎动物新生母细胞中提供了干细胞特异性的第二层保护。这些发现揭示了PIWI蛋白和PIWI相互作用RNA(PiRNAs)在干细胞生物学和细胞分化中的深远作用。染色质重组是细胞分化的重要组成部分,但有可能重新激活沉默的重复元件。Li等人。研究表明,浮游生物使用核PIWI蛋白的持续监视来伴随染色质从多能细胞到分化细胞的转变,这对浮游动物令人印象深刻的再生和动态平衡至关重要。
PIWI proteins are known as mediators of transposon silencing in animal germlines but are also found in adult pluripotent stem cells of highly regenerative animals, where they are essential for regeneration. Study of the nuclear PIWI protein SMEDWI-2 in the planarian somatic stem cell system reveals an intricate interplay between transposons and cell differentiation in which a subset of transposons is inevitably activated during cell differentiation, and the PIWI protein is required to regain control. Absence of SMEDWI-2 leads to tissue-specific transposon derepression related to cell-type-specific chromatin remodeling events and in addition causes reduced accessibility of lineage-specific genes and defective cell differentiation, resulting in fatal tissue dysfunction. Finally, we show that additional PIWI proteins provide a stem-cell-specific second layer of protection in planarian neoblasts. These findings reveal a far-reaching role of PIWI proteins and PIWI-interacting RNAs (piRNAs) in stem cell biology and cell differentiation. Chromatin reorganization is an essential part of cell differentiation but risks reactivation of silenced repetitive elements. Li et al. show that planarians use continuous surveillance by a nuclear PIWI protein to chaperone the chromatin transition from pluripotent to differentiated cell, which is crucial for the planarian’s impressive regeneration and homeostasis.
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