Journal
CELL STEM CELL
Volume 23, Issue 4, Pages 599-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2018.08.007
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Funding
- National Key R&D Program of China [2017YFA0105001, 2016YFC1000606, 2017YFA0102702, 2017YFA0103403]
- National Natural Science Foundation of China [31625018, 81521002, 31671544, 31371506, 81401191, 81570101]
- Science and Technology Planning Project of Guangdong Province, China [2016A020214020]
- China Postdoctoral Science Foundation [2017M622728]
- FACS
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Spermatogenesis generates mature male gametes and is critical for the proper transmission of genetic information between generations. However, the developmental landscapes of human spermatogenesis remain unknown. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis for 2,854 testicular cells from donors with normal spermatogenesis and 174 testicular cells from one nonobstructive azoospermia (NOA) donor. A hierarchical model was established, which was characterized by the sequential and stepwise development of three spermatogonia subtypes, seven spermatocyte subtypes, and four spermatid subtypes. Further analysis identified several stage-specific marker genes of human germ cells, such as HMGA1, PIWIL4, TEX29, SCML1, and CCDC112. Moreover, we identified altered gene expression patterns in the testicular somatic cells of one NOA patient via scRNA-seq analysis, paving the way for further diagnosis of male infertility. Our work allows for the reconstruction of transcriptional programs inherent to sequential cell fate transition during human spermatogenesis and has implications for deciphering male-related reproductive disorders.
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