Single-cell RNA-Seq Resolves Cellular Heterogeneity and Transcriptional Dynamics in Spermatogonial Stem Cells Establishment
Single-cell RNA-Seq Resolves Cellular Heterogeneity and Transcriptional Dynamics in Spermatogonial Stem Cells Establishment
Summary The transition of gonocytes to spermatogonia and subsequent differentiation provide the foundation of spermatogenesis. However, systematic understanding on the cellular and molecular basis of this process is still limited, mainly impeded by the asynchrony in development and the lack of stage-specific markers. Using single-cell RNA sequencing on Oct4-GFP+/KIT- cells isolated from PND5.5 mice, we dissected the cellular heterogeneity and established molecular regulations. We demonstrated that gonocyte-spermatogonial transition was characterized by gene expression change related to apoptosis, cell cycle progression, and regulation of migration processes. Pseudotime analysis reconstructed developmental dynamics of the spermatogonial populations and unraveled sequential cellular and molecular transitions. We also identified CD87 as a neonatal stem cell marker which are potentially involved in the intial establishment of SSC pool. Lastly, we uncovered an unexpected subpopulation of spermatogonia primed to differentiation within the undifferentiated compartment, which is characterized by the lack of self-renewal genes and enhanced Oct4 expression and retinoic acid signaling response. Our study thus provides a novel understanding of cellular and molecular changes during spermatogonial establishment.
Lee Tin-Lap、Sang Tang Nelson Leung、Fung Jacqueline、Ng Shuk Han、Shui Luk Alfred Chun、Liao Jinyue、Tu Jiajie、Qian Yan、Feng Bo、Fouchet Pierre、Chan Wai-Yee
Developmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||The Chinese University of Hong Kong ¨C Shandong University (CUHK-SDU) Joint Laboratory on Reproductive Genetics||Key Laboratory for Regenerative Medicine (Jinan University ¨C The Chinese University of Hong Kong), Ministry of Education of the People?ˉs Republic of China||Joint CUHK-UoS (University of Southampton) Joint Laboratories for Stem Cells and Regenerative Medicine, The Chinese Univesrity of Hong KongDepartment of Chemical Pathology, The Chinese University of Hong KongDevelopmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||The Chinese University of Hong Kong ¨C Shandong University (CUHK-SDU) Joint Laboratory on Reproductive GeneticsDevelopmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||The Chinese University of Hong Kong ¨C Shandong University (CUHK-SDU) Joint Laboratory on Reproductive GeneticsDevelopmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||The Chinese University of Hong Kong ¨C Shandong University (CUHK-SDU) Joint Laboratory on Reproductive GeneticsDevelopmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||The Chinese University of Hong Kong ¨C Shandong University (CUHK-SDU) Joint Laboratory on Reproductive GeneticsDevelopmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||The Chinese University of Hong Kong ¨C Shandong University (CUHK-SDU) Joint Laboratory on Reproductive GeneticsDevelopmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||The Chinese University of Hong Kong ¨C Shandong University (CUHK-SDU) Joint Laboratory on Reproductive GeneticsDevelopmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||SBS Core Laboratory, CUHK Shenzhen Research InstituteCommissariat ¨¤ l?ˉEnergie Atomique, Direction des Sciences du Vivant, Institut de Radiobiologie Cellulaire ET Mol¨|culaire, Laboratoire Gam¨|togen¨¨se||Institut National de la Sant¨| ET de la Recherche M¨|dicale||Universit¨| Paris-Diderot||Universit¨| Paris-SudDevelopmental and Regenerative Biology Program, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong||The Chinese University of Hong Kong ¨C Shandong University (CUHK-SDU) Joint Laboratory on Reproductive Genetics||Key Laboratory for Regenerative Medicine (Jinan University ¨C The Chinese University of Hong Kong), Ministry of Education of the People?ˉs Republic of China||Joint CUHK-UoS (University of Southampton) Joint Laboratories for Stem Cells and Regenerative Medicine, The Chinese Univesrity of Hong Kong
细胞生物学分子生物学基础医学
Single celltranscriptomesspermatogoniadifferentiationdevelopment
Lee Tin-Lap,Sang Tang Nelson Leung,Fung Jacqueline,Ng Shuk Han,Shui Luk Alfred Chun,Liao Jinyue,Tu Jiajie,Qian Yan,Feng Bo,Fouchet Pierre,Chan Wai-Yee.Single-cell RNA-Seq Resolves Cellular Heterogeneity and Transcriptional Dynamics in Spermatogonial Stem Cells Establishment[EB/OL].(2025-03-28)[2025-06-07].https://www.biorxiv.org/content/10.1101/194696.点此复制
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