Single-cell analyses reveal impaired type B spermatogonia differentiation and meiotic entry in C-Nap1-null testes  

作　　者：Junlin Li Liheng Yang Liansheng Li Min Li Juntao Gao Li Yuan 

机构地区：[1]Medical School,University of Chinese Academy of Sciences,Beijing,China [2]Zanvyl Krieger School of Arts and Sciences,Johns Hopkins University,Baltimore,Maryland,USA [3]Viterbi School of Engineering,University of Southern California,Los Angeles,California,USA [4]Molecular Biology Laboratory,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing,China [5]Institute for TCM-X,Beijing,China [6]MOE Key Laboratory of Bioinformatics,Beijing,China [7]Bioinformatics Division,Department of Automation,BNRist,Beijing,China [8]Center for Synthetic&Systems Biology,Tsinghua University,Beijing,China

出　　处：《Quantitative Biology》2025年第1期63-75,共13页定量生物学(英文版)

基　　金：The Fundamental Research Funds for the Central Universities,Grant/Award Number:E1E43201X2;The Beijing Municipal Natural Science Foundation,Grant/Award Number:Z200021;The CAS Interdisciplinary Innovation Team,Grant/Award Number:JCTD-2020-04;The National Key Research and Development Program of China,Grant/Award Numbers:2021YFE0201100,2022YFA1103401;The National Natural Science Foundation of China,Grant/Award Number:31872839。

摘　　要：Sperm development is critical for male reproductive capability;any disruption during the process of spermatogenesis will result in male infertility.In this research,we used the C-Nap1 encoded by the gene of Cep250 knockout mouse line as the model to evaluate the impact of absent C-Nap1 on spermatogenesis.To investigate the interaction between C-Nap1 and spermatogenesis,weutilized single-cellRNAsequencing to analyze 10,332C-Nap1t/t and 13,308C-Nap1^(−/−)testicular cells.Weidentified five main cell types within seminiferous tubules,including spermatogonia,Sertoli cells,spermatogonia stem cells,Leydig cells,and spermatocytes.We found a critical reduction in testicular spermatogonia and spermatocytes in C-Nap1-null testes,compared to its C-Nap1t/t controls.By combining uniform manifold approximation and projection clustering and psedotime ordering,we distinguished five spermatogonial stages/subtypes,demonstrating that type B spermatogonia differentiation and meiotic initiation are impaired during C-Nap1-null spermatogenesis.Following gene ontology enrichment analysis,meiosis-specific genes downregulated in the C-Nap1^(−/−)testicular cells were further verified by reverse transcription polymerase chain reaction(RT-PCR).Based on the differential gene expression,certain downregulated genes such as Ctnnb1 and Aurka encoding C-Nap1-binding potentialβ-Catenin and Aurka are encountered,which may account for defective type B spermatogonia differentiation and meiotic entry in C-Nap1-null testes.

关 键 词：C-Nap1 mouse testis single-cell RNA sequencing SPERMATOGENESIS 

分 类 号：R69[医药卫生—泌尿科学]