NOTCH signaling pathway is required for bovine early embryonic development
NOTCH signaling pathway is required for bovine early embryonic development
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NOTCH信号通路是牛早期胚胎发育所必需的
DOI：
10.1093/biolre/ioab056
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发表时间：
2021-03-24
影响因子：
3.6
通讯作者：
Zhang, Kun
中科院分区：
文献类型：
--
作者：
Li, Shuang;Shi, Yan;Zhang, Kun
摘要NOTCH信号通路在调控细胞谱系分化和细胞凋亡等多种生物学过程中起着重要作用。已经在哺乳动物植入前胚胎中鉴定了NOTCH途径的多个组分。然而，NOTCH通路在早期胚胎发育中的确切作用知之甚少，特别是在大型动物中。在这里，我们表明，编码NOTCH通路的关键转录本的基因的表达是动态的，在整个早期胚胎发育。我们还证实了活性NOTCH1和RBPJ的存在。通过使用药理学和RNA干扰工具，我们证明了NOTCH途径是牛早期胚胎正常发育所必需的。这种功能性后果可能部分归因于主要的转录介质，免疫球蛋白κ J区的转录信号结合蛋白（RBPJ），其缺陷也会损害胚胎质量。事实上，NOTCH1和RBPJ敲低均导致组蛋白H3丝氨酸10磷酸化（pH3S10，有丝分裂标志物）阳性卵裂球显著增加，表明有丝分裂时细胞周期停滞。重要的是，RNA测序分析表明，无论是NOTCH1或RBPJ耗尽触发减少H1FOO，编码卵母细胞特异性接头组蛋白H1变体。有趣的是，耗尽H1FOO会对早期胚胎的发育能力产生不利影响，与NOTCH 1抑制类似。总之，我们的研究结果揭示了NOTCH通路在调节牛植入前发育中的关键作用，可能是通过控制细胞增殖和维持H1FOO表达。NOTCH信号通路在牛早期胚胎发育过程中起着不可或缺的作用，其可能通过调节细胞增殖和H1FOO的表达来介导。
Abstract The NOTCH signaling pathway plays an important role in regulating various biological processes, including lineage specification and apoptosis. Multiple components of the NOTCH pathway have been identified in mammalian preimplantation embryos. However, the precise role of the NOTCH pathway in early embryonic development is poorly understood, especially in large animals. Here, we show that the expression of genes encoding key transcripts of the NOTCH pathway is dynamic throughout early embryonic development. We also confirm the presence of active NOTCH1 and RBPJ. By using pharmacological and RNA interference tools, we demonstrate that the NOTCH pathway is required for the proper development of bovine early embryos. This functional consequence could be partly attributed to the major transcriptional mediator, Recombination Signal Binding Protein For Immunoglobulin Kappa J Region (RBPJ), whose deficiency also compromised the embryo quality. Indeed, both NOTCH1 and RBPJ knockdown cause a significant increase of histone H3 serine 10 phosphorylation (pH3S10, a mitosis marker) positive blastomeres, suggesting a cell cycle arrest at mitosis. Importantly, RNA sequencing analyses reveal that either NOTCH1 or RBPJ depletion triggers a reduction in H1FOO that encodes the oocyte-specific linker histone H1 variant. Interestingly, depleting H1FOO results in detrimental effects on the developmental competence of early embryos, similar with NOTCH1 inhibition. Overall, our results reveal a crucial role for NOTCH pathway in regulating bovine preimplantation development, likely by controlling cell proliferation and maintaining H1FOO expression. Summary sentence NOTCH signaling pathway plays an indispensable role in bovine early embryonic development, which is potentially mediated by regulation of cell proliferation and expression of H1FOO.