Functional roles of the chromatin remodeler SMARCA5 in mouse and bovine preimplantation embryos
Functional roles of the chromatin remodeler SMARCA5 in mouse and bovine preimplantation embryos
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染色质重塑蛋白 SMARCA5 在小鼠和牛植入前胚胎中的功能作用
DOI：
10.1093/biolre/ioab081
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发表时间：
2021-04-23
影响因子：
3.6
通讯作者：
Zhang, Kun
中科院分区：
文献类型：
--
作者：
Shi, Yan;Zhao, Panpan;Zhang, Kun
摘要受精后，在着床前发育过程中会发生大量的染色质重编程。越来越多的证据表明，哺乳动物的这一过程依赖于物种的调节。依赖于三磷酸腺苷的染色质重塑因子SMARCA5(也称为SNF2H)是小鼠围着床期发育所必需的。然而，SMARCA5在着床前发育中的具体功能以及它在物种之间是否保守仍不清楚。在此，对公共RNA-seq数据集的比较分析表明，SMARCA5在小鼠、牛、人和猪的卵母细胞成熟和植入前发育过程中普遍表达，并具有物种特异性模式。免疫染色分析进一步描述了SMARCA5在小鼠和牛模型中的时间和空间变化。SiRNA介导的SMARCA5缺失降低了小鼠着床前胚胎的发育能力，并损害了内细胞团的规范和分化。事实上，在SMARCA5缺陷的囊胚中，OCT4并不局限于内细胞团，上胚层和原始内胚层的形成受到干扰，NANOG和SOX17减少。RNA-seq分析表明，SMARCA5的缺失对桑椹胚期的转录转录影响有限，但对402个基因的调控失调，包括参与转录调控和囊胚期细胞增殖的基因。相比之下，SMARCA5的缺失不会影响整个囊胚期的发育，但会显著影响牛的囊胚质量。牛囊胚中原始内胚层的形成被极大地破坏，GATA6减少。总体而言，我们的研究证明了SMARCA5在促进小鼠和牛的植入前发育方面的重要性，同时存在物种特异性的影响。在小鼠和牛身上，染色质重构体SMARCA5是植入前发育所必需的，具有物种特异性效应。
Abstract Upon fertilization, extensive chromatin reprogramming occurs during preimplantation development. Growing evidence reveals species-dependent regulations of this process in mammals. ATP-dependent chromatin remodeling factor SMARCA5 (also known as SNF2H) is required for peri-implantation development in mice. However, the specific functional role of SMARCA5 in preimplantation development and if it is conserved among species remain unclear. Herein, comparative analysis of public RNA-seq datasets reveals that SMARCA5 is universally expressed during oocyte maturation and preimplantation development in mice, cattle, humans, and pigs with species-specific patterns. Immunostaining analysis further describes the temporal and spatial changes of SMARCA5 in both mouse and bovine models. siRNA-mediated SMARCA5 depletion reduces the developmental capability and compromises the specification and differentiation of inner cell mass in mouse preimplantation embryos. Indeed, OCT4 is not restricted into the inner cell mass and the formation of epiblast and primitive endoderm disturbed with reduced NANOG and SOX17 in SMARCA5-deficient blastocysts. RNA-seq analysis shows SMARCA5 depletion causes limited effects on the transcriptomics at the morula stage, however, dysregulates 402 genes, including genes involved in transcription regulation and cell proliferation at the blastocyst stage in mice. By comparison, SMARCA5 depletion does not affect the development through the blastocyst stage but significantly compromises the blastocyst quality in cattle. Primitive endoderm formation is greatly disrupted with reduced GATA6 in bovine blastocysts. Overall, our studies demonstrate the importance of SMARCA5 in fostering the preimplantation development in mice and cattle while there are species-specific effects. Summary sentence The chromatin remodeler SMARCA5 is required for preimplantation development with species-specific effects in mice and cattle.