整合单细胞转录组学和网络建模揭示绵羊合子基因组激活的模块化调节因子。

IF 3.6 3区 生物学 Q1 BIOLOGY
Xiaopeng Li, Peng Niu, Kai Hu, Xueyan Wang, Fei Huang, Pengyan Song, Qinghua Gao, Di Fang
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引用次数: 0

摘要

合子基因组激活(ZGA)标志着发育早期从依赖母体转录物到启动胚胎转录的关键转变。尽管在模式物种中进行了广泛的表征,绵羊ZGA的调控框架仍然不明确。在这里,我们将单细胞RNA测序(Smart-seq2)应用于体内和体外来源于8、16和32细胞期的绵羊胚胎。差异表达分析显示,在8-细胞与16-细胞、16-细胞与32-细胞和8-细胞与32-细胞的转化过程中,分别有114、1628和1465个基因发生了改变,核心多能因子SOX2、NANOG、POU5F1和KLF4在ZGA期间上调。为了揭示协调的调控模块,我们使用WGCNA构建了一个加权基因共表达网络,确定了与发育进程最密切相关的MEred模块(r = 0.48, p = 8.6 × 10-14)。将MERed基因整合到STRING v11蛋白-蛋白相互作用网络中,为群落检测提供了高置信度的框架。Louvain划分描绘了两个离散的群落:群落0富集er -高尔基体囊泡介导的转运、跨膜转运和细胞骨架动力学,表明在膜蛋白加工、分泌和早期信号传导中起作用;社区1在G2/M细胞周期转换和RNA剪接/加工中富集,表明zga后细胞分裂和转录物成熟有一个协调的网络。总之,这些综合分析揭示了绵羊ZGA的模块化调控结构,并为解剖该物种的早期胚胎发育提供了一个框架。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrative Single-Cell Transcriptomics and Network Modeling Reveal Modular Regulators of Sheep Zygotic Genome Activation.

Zygotic genome activation (ZGA) marks the critical transition from reliance on maternal transcripts to the initiation of embryonic transcription early in development. Despite extensive characterization in model species, the regulatory framework of ZGA in sheep remains poorly defined. Here, we applied single-cell RNA sequencing (Smart-seq2) to in vivo- and in vitro-derived sheep embryos at the 8-, 16-, and 32-cell stages. Differential expression analysis revealed 114, 1628, and 1465 genes altered in the 8- vs. 16-, 16- vs. 32-, and 8- vs. 32-cell transitions, respectively, with the core pluripotency factors SOX2, NANOG, POU5F1, and KLF4 upregulated during major ZGA. To uncover coordinated regulatory modules, we constructed a weighted gene co-expression network using WGCNA, identifying the MEred module as most tightly correlated with developmental progression (r = 0.48, p = 8.6 × 10-14). The integration of MERed genes into the STRING v11 protein-protein interaction network furnished a high-confidence scaffold for community detection. Louvain partitioning delineated two discrete communities: Community 0 was enriched in ER-Golgi vesicle-mediated transport, transmembrane transport, and cytoskeletal dynamics, suggesting roles in membrane protein processing, secretion, and early signaling; Community 1 was enriched in G2/M cell-cycle transition and RNA splicing/processing, indicating a coordinated network for accurate post-ZGA cell division and transcript maturation. Together, these integrated analyses reveal a modular regulatory architecture underlying sheep ZGA and provide a framework for dissecting early embryonic development in this species.

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来源期刊
Biology-Basel
Biology-Basel Biological Science-Biological Science
CiteScore
5.70
自引率
4.80%
发文量
1618
审稿时长
11 weeks
期刊介绍: Biology (ISSN 2079-7737) is an international, peer-reviewed, quick-refereeing open access journal of Biological Science published by MDPI online. It publishes reviews, research papers and communications in all areas of biology and at the interface of related disciplines. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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