A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool.
A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool.
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DOI：
10.1016/j.stemcr.2021.04.003
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发表时间：
2021-06-08
影响因子：
5.9
通讯作者：
Lord T
中科院分区：
文献类型：
--
作者：
Cafe SL;Skerrett-Byrne DA;De Oliveira CS;Nixon B;Oatley MJ;Oatley JM;Lord T
精原干细胞（SSC）群体的维持和自我更新是男性生育的基石。在这里，我们已经确定了核小体重塑蛋白CHD 4在调节SSC功能中的关键作用。基因表达分析显示，CHD 4表达在小鼠睾丸中的SSC群体中高度富集。使用精原细胞移植技术，它被确定为Chd 4表达的损失显着损害SSC再生能力，导致受体睾丸的定殖减少约50%。scRNA-seq比较显示Chd 4敲低后“自我更新”基因的表达减少，沿着特征祖基因的表达增加。免疫共沉淀分析表明，CHD 4调节精原细胞的基因表达，不仅通过其传统的协会与重塑复合物NuRD，但也通过与GDNF反应性转录因子SALL 4的相互作用。累积起来，这项研究的结果描绘了一个以前不受重视的作用，CHD 4在控制精原细胞池的命运决定。CHD 4在小鼠睾丸精原干细胞中高度表达CHD 4表达是维持精原干细胞所必需的CHD 4与SALL 4和NuRD相互作用以激活“自我更新”基因的表达在这篇文章中，Lord和同事表明重塑蛋白CHD 4在精原干细胞（SSC）中高度表达，并且在功能上是SSC维持所必需的。作者证明，CHD 4与NuRD复合物和SALL 4相互作用，以激活“自我更新”基因（如Gfra 1）的表达。
Maintenance and self-renewal of the spermatogonial stem cell (SSC) population is the cornerstone of male fertility. Here, we have identified a key role for the nucleosome remodeling protein CHD4 in regulating SSC function. Gene expression analyses revealed that CHD4 expression is highly enriched in the SSC population in the mouse testis. Using spermatogonial transplantation techniques it was established that loss of Chd4 expression significantly impairs SSC regenerative capacity, causing a ∼50% reduction in colonization of recipient testes. An scRNA-seq comparison revealed reduced expression of “self-renewal” genes following Chd4 knockdown, along with increased expression of signature progenitor genes. Co-immunoprecipitation analyses demonstrated that CHD4 regulates gene expression in spermatogonia not only through its traditional association with the remodeling complex NuRD, but also via interaction with the GDNF-responsive transcription factor SALL4. Cumulatively, the results of this study depict a previously unappreciated role for CHD4 in controlling fate decisions in the spermatogonial pool. CHD4 is highly expressed in spermatogonial stem cells in the mouse testis CHD4 expression is required for spermatogonial stem cell maintenance CHD4 interacts with SALL4 and NuRD to activate expression of “self-renewal” genes In this article, Lord and colleagues show that the remodeling protein CHD4 is highly expressed in spermatogonial stem cells (SSCs), and is functionally required for SSC maintenance. The authors demonstrate that CHD4 interacts with the NuRD complex and SALL4 to activate expression of “self-renewal” genes, such as Gfra1.
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影响因子：
5.9
作者：
Chan AL;La HM;Legrand JMD;Mäkelä JA;Eichenlaub M;De Seram M;Ramialison M;Hobbs RM
通讯作者：
Hobbs RM
影响因子：
44.1
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影响因子：
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通讯作者：
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影响因子：
23.9
作者：
Sanchez CG;Teixeira FK;Czech B;Preall JB;Zamparini AL;Seifert JR;Malone CD;Hannon GJ;Lehmann R
通讯作者：
Lehmann R
影响因子：
10.5
作者：
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通讯作者：
Georgopoulos, Katia