Proteome landscape and spatial map of mouse primordial germ cells

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oteome landscape and spatial map of mouse primordial germ cells 1

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Pan Wang , Yilong Miao , Xiao-Han Li , Na Zhang , Qilong Wang , Wei Yue 2 2* 1,3,4 1,3,4* Shao-Chen Sun , Bo Xiong , Jie Qiao & Mo Li

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Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China; College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China; 3 National Clinical Research Center for Obstetrics and Gynecology, Beijing 100191, China; 4 Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China 2

Received April 6, 2020; accepted June 19, 2020; published online August 26, 2020

Primordial germ cells (PGCs) are precursors of both male and female gametes as fundamental materials for organism development. The transcriptome, methylome, and chromatin accessibility profiles of PGCs in both mice and humans have been recently reported. However, little is known about the characteristics of PGCs at the protein levels, which directly exert cellular functions. Here, we construct landscapes of both proteome and 3D spatial distribution of mouse PGCs at E11.5, E13.5 and E16.5 days, the three critical developmental windows for PGCs’ sex differentiation, female meiosis initiation and male mitotic arrest. In each developmental stage of PGCs, nearly 2,000–3,000 proteins are identified, among which specific functional pathways such as oxidative phosphorylation, DNA damage repair, and meiotic cell cycle are involved for different events during PGCs development. Interestingly, by 3D modeling we find that PGCs spatially cluster into around 1,300 nests in genital ridge at E11.5 and the nest number is not increased by the exponential proliferation of PGCs. Comparative analysis of our proteomic data with published transcriptomic data does not show a close correlation, meaning that the practically executive factors are beyond the transcriptome. Thus, our work offers a valuable resource for the systematic investigations of PGC development at protein level and spatial map. PGCs, proteome, spatial map, sex differentiation, meiosis Citation:

Wang, P., Miao, Y., Li, X.H., Zhang, N., Wang, Q., Yue, W., Sun, S.C., Xiong, B., Qiao, J., and Li, M. (2020). Proteome landscape and spatial map of mouse primordial germ cells. Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1762-2

INTRODUCTION In organisms with sexual reproduction, primordial germ cells (PGCs) are embryonic precursors of sperm and egg that pass on genetic and epigenetic information to subsequent generations (Ewen and Koopman, 2010; Hayashi et al., 2007). PGC specification in mammals involves a series of key molecular and cellular events that turn off the somatic program and switch on the germline program to separate the *Corresponding authors (Mo Li, email: [email protected]; Bo Xiong, email: [email protected])

germline from the somatic lineages (Martínez-Arroyo et al., 2014). In mouse model, PGCs derive from a small group of proximal epiblast cells and b