College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
BGI-Shenzhen, Shenzhen 518083, China.
Gigascience. 2022 Dec 28;12. doi: 10.1093/gigascience/giad038. Epub 2023 May 25.
Early post-implantation development, especially gastrulation in primates, is accompanied by extensive drastic chromatin reorganization, which remains largely elusive.
To delineate the global chromatin landscape and understand the molecular dynamics during this period, a single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) was applied to in vitro cultured cynomolgus monkey (Macaca fascicularis, hereafter referred to as monkey) embryos to investigate the chromatin status. First, we delineated the cis-regulatory interactions and identified the regulatory networks and critical transcription factors involved in the epiblast (EPI), hypoblast, and trophectoderm/trophoblast (TE) lineage specification. Second, we observed that the chromatin opening of some genome regions preceded the gene expression during EPI and trophoblast specification. Third, we identified the opposing roles of FGF and BMP signaling in pluripotency regulation during EPI specification. Finally, we revealed the similarity between EPI and TE in gene expression profiles and demonstrated that PATZ1 and NR2F2 were involved in EPI and trophoblast specification during monkey post-implantation development.
Our findings provide a useful resource and insights into dissecting the transcriptional regulatory machinery during primate post-implantation development.
早期胚胎植入后发育，尤其是灵长类动物的原肠胚形成，伴随着广泛而剧烈的染色质重排，但这一过程在很大程度上仍难以捉摸。
为了描绘这一时期的全基因组染色质景观并理解其分子动态，我们应用转座酶可及染色质测序（scATAC-seq）的单细胞分析，对体外培养的食蟹猴（Macaca fascicularis，以下简称猴）胚胎进行研究，以调查染色质状态。首先，我们描绘了顺式调控相互作用，并鉴定了涉及上胚层（EPI）、下胚层和滋养外胚层/滋养层（TE）谱系特化的调控网络和关键转录因子。其次，我们观察到一些基因组区域的染色质开放性在 EPI 和滋养层特化过程中的基因表达之前。第三，我们发现 FGF 和 BMP 信号在 EPI 特化过程中的多能性调控中具有相反的作用。最后，我们揭示了 EPI 和 TE 在基因表达谱上的相似性，并证明 PATZ1 和 NR2F2 参与了猴胚后植入发育过程中的 EPI 和滋养层特化。
我们的发现为解析灵长类动物胚胎植入后发育过程中的转录调控机制提供了有用的资源和见解。
