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Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes.
Sci China Life Sci. 2020 07; 63(7):1006-1015.SC

Abstract

Being infected by SARS-CoV-2 may cause damage to multiple organs in patients, such as the lung, liver and heart. Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is also expressed in human male testes. This suggests a potential risk in human male reproductive system. However, the characteristics of ACE2-positive cells and the expression of other SARS-CoV-2 process-related genes are still worthy of further investigation. Here, we performed singlecell RNA seq (scRNA-seq) analysis on 853 male embryo primordial germ cells (PGCs) and 2,854 normal testis cells to assess the effects of the SARS-CoV-2 virus on the male reproductive system from embryonic stage to adulthood. We also collected and constructed the scRNA-seq library on 228 Sertoli cells from three non-obstructive azoospermia (NOA) patients to assess the effects at disease state. We found that ACE2 expressing cells existed in almost all testis cell types and Sertoli cells had highest expression level and positive cells ratio. Moreover, ACE2 was also expressed in human male PGCs. In adulthood, the level of ACE2 expression decreased with the increase of age. We also found that ACE2 positive cells had high expressions of stress response and immune activation-related genes. Interestingly, some potential SARS-CoV-2 process-related genes such as TMPRSS2, BSG, CTSL and CTSB had different expression patterns in the same cell type. Furthermore, ACE2 expression level in NOA donors' Sertoli cells was significantly decreased. Our work would help to assess the risk of SARS-CoV-2 infection in the male reproductive system.

Authors+Show Affiliations

Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, 100871, China. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China.Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, 100871, China. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.Department of Urology, Peking University Third Hospital, Beijing, 100191, China.Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, 100871, China. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, 100871, China. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. National Clinical Research Center for Obstetrics and Gynecology, Beijing, 100191, China. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China.Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, 100871, China. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, 100871, China. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, 100871, China. yanliyingkind@aliyun.com. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. yanliyingkind@aliyun.com. National Clinical Research Center for Obstetrics and Gynecology, Beijing, 100191, China. yanliyingkind@aliyun.com. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China. yanliyingkind@aliyun.com.Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, 100871, China. jie.qiao@263.net. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China. jie.qiao@263.net. National Clinical Research Center for Obstetrics and Gynecology, Beijing, 100191, China. jie.qiao@263.net. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China. jie.qiao@263.net. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. jie.qiao@263.net.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32361911

Citation

Liu, Xixi, et al. "Single-cell Transcriptome Analysis of the Novel Coronavirus (SARS-CoV-2) Associated Gene ACE2 Expression in Normal and Non-obstructive Azoospermia (NOA) Human Male Testes." Science China. Life Sciences, vol. 63, no. 7, 2020, pp. 1006-1015.
Liu X, Chen Y, Tang W, et al. Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes. Sci China Life Sci. 2020;63(7):1006-1015.
Liu, X., Chen, Y., Tang, W., Zhang, L., Chen, W., Yan, Z., Yuan, P., Yang, M., Kong, S., Yan, L., & Qiao, J. (2020). Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes. Science China. Life Sciences, 63(7), 1006-1015. https://doi.org/10.1007/s11427-020-1705-0
Liu X, et al. Single-cell Transcriptome Analysis of the Novel Coronavirus (SARS-CoV-2) Associated Gene ACE2 Expression in Normal and Non-obstructive Azoospermia (NOA) Human Male Testes. Sci China Life Sci. 2020;63(7):1006-1015. PubMed PMID: 32361911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes. AU - Liu,Xixi, AU - Chen,Yidong, AU - Tang,Wenhao, AU - Zhang,Li, AU - Chen,Wei, AU - Yan,Zhiqiang, AU - Yuan,Peng, AU - Yang,Ming, AU - Kong,Siming, AU - Yan,Liying, AU - Qiao,Jie, Y1 - 2020/04/30/ PY - 2020/03/31/received PY - 2020/04/21/accepted PY - 2020/5/4/pubmed PY - 2020/7/1/medline PY - 2020/5/4/entrez KW - ACE2 KW - COVID-19 KW - NOA KW - SARS-CoV-2 KW - TMPRSS2 KW - adult KW - fetal KW - normal KW - testis cells SP - 1006 EP - 1015 JF - Science China. Life sciences JO - Sci China Life Sci VL - 63 IS - 7 N2 - Being infected by SARS-CoV-2 may cause damage to multiple organs in patients, such as the lung, liver and heart. Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is also expressed in human male testes. This suggests a potential risk in human male reproductive system. However, the characteristics of ACE2-positive cells and the expression of other SARS-CoV-2 process-related genes are still worthy of further investigation. Here, we performed singlecell RNA seq (scRNA-seq) analysis on 853 male embryo primordial germ cells (PGCs) and 2,854 normal testis cells to assess the effects of the SARS-CoV-2 virus on the male reproductive system from embryonic stage to adulthood. We also collected and constructed the scRNA-seq library on 228 Sertoli cells from three non-obstructive azoospermia (NOA) patients to assess the effects at disease state. We found that ACE2 expressing cells existed in almost all testis cell types and Sertoli cells had highest expression level and positive cells ratio. Moreover, ACE2 was also expressed in human male PGCs. In adulthood, the level of ACE2 expression decreased with the increase of age. We also found that ACE2 positive cells had high expressions of stress response and immune activation-related genes. Interestingly, some potential SARS-CoV-2 process-related genes such as TMPRSS2, BSG, CTSL and CTSB had different expression patterns in the same cell type. Furthermore, ACE2 expression level in NOA donors' Sertoli cells was significantly decreased. Our work would help to assess the risk of SARS-CoV-2 infection in the male reproductive system. SN - 1869-1889 UR - https://www.unboundmedicine.com/medline/citation/32361911/Single_cell_transcriptome_analysis_of_the_novel_coronavirus__SARS_CoV_2__associated_gene_ACE2_expression_in_normal_and_non_obstructive_azoospermia__NOA__human_male_testes_ L2 - https://dx.doi.org/10.1007/s11427-020-1705-0 DB - PRIME DP - Unbound Medicine ER -