Single-cell RNA sequencing reveals regulation of fetal ovary development in the monkey (Macaca fascicularis).

Zheng-Hui Zhao, Chun-Yang Li, Tie-Gang Meng, Yan Wang, Wen-Bo Liu, Ang Li, Yi-Jun Cai, Yi Hou, Heide Schatten, Zhen-Bo Wang, Qing-Yuan Sun, Qiang Sun
Author Information
  1. Zheng-Hui Zhao: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  2. Chun-Yang Li: Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, 200031, Shanghai, China.
  3. Tie-Gang Meng: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  4. Yan Wang: Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, 200031, Shanghai, China.
  5. Wen-Bo Liu: Department of Reproductive Medicine Center, Third Affiliated Hospital of Guangzhou Medical University, 510150, Guangzhou, Guangdong, China.
  6. Ang Li: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  7. Yi-Jun Cai: Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, 200031, Shanghai, China.
  8. Yi Hou: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  9. Heide Schatten: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA.
  10. Zhen-Bo Wang: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China. ORCID
  11. Qing-Yuan Sun: Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, 510317, Guangzhou, Guangdong, China. sunqy@gd2h.org.cn. ORCID
  12. Qiang Sun: Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, 200031, Shanghai, China. qsun@ion.ac.cn.

Abstract

Germ cells are vital for reproduction and heredity. However, the mechanisms underlying female germ cell development in primates, especially in late embryonic stages, remain elusive. Here, we performed single-cell RNA sequencing of 12,471 cells from whole fetal ovaries, and explored the communications between germ cells and niche cells. We depicted the two waves of oogenesis at single-cell resolution and demonstrated that progenitor theca cells exhibit similar characteristics to Leydig cells in fetal monkey ovaries. Notably, we found that ZGLP1 displays differentially expressed patterns between mouse and monkey, which is not overlapped with NANOG in monkey germ cells, suggesting its role in meiosis entry but not in activating oogenic program in primates. Furthermore, the majority of germ cell clusters that sharply express PRDM9 and SPO11 might undergo apoptosis after cyst breakdown, leading to germ cell attrition. Overall, our work provides new insights into the molecular and cellular basis of primate fetal ovary development at single-cell resolution.

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Grants

  1. 31801245/National Natural Science Foundation of China (National Science Foundation of China)
  2. 31825018/National Natural Science Foundation of China (National Science Foundation of China)