单细胞 RNA-Seq 揭示了原始卵泡形成过程中小鼠生殖细胞中高度协调的转录程序,Aging Cell

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单细胞 RNA-Seq 揭示了原始卵泡形成过程中小鼠生殖细胞中高度协调的转录程序
Aging Cell ( IF 8.0 ) Pub Date : 2021-06-26 , DOI: 10.1111/acel.13424
Yuanlin He _{1,

2} , Qiuzhen Chen _{1,

3,

4} , Juncheng Dai ₂ , Yiqiang Cui ₁ , Chi Zhang ₁ , Xidong Wen ₁ , Jiazhao Li ₁ , Yue Xiao ₁ , Xiaoxu Peng ₁ , Mingxi Liu ₁ , Bin Shen ₁ , Jiahao Sha ₁ , Zhibin Hu _{1,

2} , Jing Li ₁ , Wenjie Shu ₃

Affiliation

哺乳动物原始卵泡的组装是卵巢生物学中最关键的过程之一。它直接影响女性在整个生殖生命中可获得的卵母细胞数量。原始卵泡的过早耗竭导致卵巢病理学原发性卵巢功能不全（POI）。为了描绘卵母细胞在此过程中的发育轨迹和调控机制，我们对来自新生儿 (P0.5) 卵巢的单个生殖细胞进行了 RNA-seq。三个细胞簇被分类，它们对应于新生儿卵巢中的三种细胞状态（生殖细胞囊肿、囊肿破裂和卵泡）。通过Monocle分析，构建了一条卵母细胞发育的统一轨迹，一系列基因沿着伪时间线呈现动态变化。基因本体术语富集显示减数分裂相关基因显着减少，卵母细胞特异性基因显着增加，这标志着从生殖细胞向功能性卵母细胞的转变。然后，我们通过使用单细胞调节网络推理和聚类 (SCENIC) 算法建立了一个调节子网络，并确定了可能在卵泡形成过程中维持转录程序的候选转录因子。以下功能研究进一步揭示了已识别调节子的差异调节然后，我们通过使用单细胞调节网络推理和聚类 (SCENIC) 算法建立了一个调节子网络，并确定了可能在卵泡形成过程中维持转录程序的候选转录因子。以下功能研究进一步揭示了已识别调节子的差异调节然后，我们通过使用单细胞调节网络推理和聚类 (SCENIC) 算法建立了一个调节子网络，并确定了可能在卵泡形成过程中维持转录程序的候选转录因子。以下功能研究进一步揭示了已识别调节子的差异调节Id2及其家族成员Id1，关于使用 siRNA 敲低和转基因小鼠模型建立原始卵泡池。总之，我们的研究系统地重建了卵母细胞中的分子级联反应，并确定了卵泡形成和发育过程中的一系列基因和分子通路。

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Single-cell RNA-Seq reveals a highly coordinated transcriptional program in mouse germ cells during primordial follicle formation

The assembly of primordial follicles in mammals represents one of the most critical processes in ovarian biology. It directly affects the number of oocytes available to a female throughout her reproductive life. Premature depletion of primordial follicles contributes to the ovarian pathology primary ovarian insufficiency (POI). To delineate the developmental trajectory and regulatory mechanisms of oocytes during the process, we performed RNA-seq on single germ cells from newborn (P0.5) ovaries. Three cell clusters were classified which corresponded to three cell states (germ cell cyst, cyst breakdown, and follicle) in the newborn ovary. By Monocle analysis, a uniform trajectory of oocyte development was built with a series of genes showed dynamic changes along the pseudo-timeline. Gene Ontology term enrichment revealed a significant decrease in meiosis-related genes and a dramatic increase in oocyte-specific genes which marked the transition from a germ cell to a functional oocyte. We then established a network of regulons by using single-cell regulatory network inference and clustering (SCENIC) algorithm and identified possible candidate transcription factors that may maintain transcription programs during follicle formation. Following functional studies further revealed the differential regulation of the identified regulon Id2 and its family member Id1, on the establishment of primordial follicle pool by using siRNA knockdown and genetic modified mouse models. In summary, our study systematically reconstructed molecular cascades in oocytes and identified a series of genes and molecular pathways in follicle formation and development.

更新日期：2021-07-16

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