Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
Sequencing Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
Int J Mol Sci. 2021 Nov 4;22(21):11955. doi: 10.3390/ijms222111955.
Human ovarian folliculogenesis is a highly regulated and complex process. Characterization of follicular cell signatures during this dynamic process is important to understand follicle fate (to grow, become dominant, or undergo atresia). The transcriptional signature of human oocytes and granulosa cells (GCs) in early-growing and ovulatory follicles have been previously described; however, that of oocytes with surrounding GCs in small antral follicles have not been studied yet. Here, we have generated a unique dataset of single-cell transcriptomics (SmartSeq2) consisting of the oocyte with surrounding GCs from several individual (non-dominant) small antral follicles isolated from adult human ovaries. We have identified two main types of (healthy) follicles, with a distinct oocyte and GC signature. Using the CellphoneDB algorithm, we then investigated the bi-directional ligand-receptor interactions regarding the transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP), wingless-type (MMTV)-integration site (WNT), NOTCH, and receptor tyrosine kinases (RTK) signaling pathways between oocyte and GCs within each antral follicle type. Our work not only revealed the diversity of small antral follicles, but also contributes to fill the gap in mapping the molecular landscape of human folliculogenesis and oogenesis.
人类卵巢卵泡发生是一个高度调控和复杂的过程。在这个动态过程中，描述卵泡细胞特征对于理解卵泡命运（生长、成为优势卵泡或发生闭锁）非常重要。人类卵母细胞和颗粒细胞（GCs）在早期生长和排卵卵泡中的转录特征已经被描述；然而，在小窦卵泡中，具有周围 GCs 的卵母细胞的转录特征尚未被研究。在这里，我们生成了一个由单细胞转录组学（SmartSeq2）组成的独特数据集，该数据集由来自成人卵巢的几个单个（非优势）小窦卵泡中分离的卵母细胞及其周围 GCs 组成。我们已经确定了两种主要类型（健康）的卵泡，具有独特的卵母细胞和 GC 特征。然后，我们使用 CellphoneDB 算法，研究了每个窦卵泡类型中卵母细胞和 GCs 之间转化生长因子-β（TGFβ）/骨形态发生蛋白（BMP）、乳腺肿瘤病毒（MMTV）整合位点（WNT）、NOTCH 和受体酪氨酸激酶（RTK）信号通路之间的双向配体-受体相互作用。我们的工作不仅揭示了小窦卵泡的多样性，而且有助于填补人类卵泡发生和卵母细胞发生分子图谱绘制的空白。
