AUTHOR=Tang Xiao-juan , Xiao Qiao-hong , Wang Xue-lin , He Yan , Tian Ya-nan , Xia Bin-tong , Guo Yang , Huang Jiao-long , Duan Peng , Tan Yan 

TITLE=Single-Cell Transcriptomics-Based Study of Transcriptional Regulatory Features in the Non-Obstructive Azoospermia Testis

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.875762

DOI=10.3389/fgene.2022.875762

ISSN=1664-8021

ABSTRACT=Abstract
18 Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. Although
19 increased number of congenital factors have been identified, the etiology in the majority of idiopathic
20 NOA (iNOA) cases remains unknown. Herein, using the single-cell RNA-Seq data sets (GSE149512)
21 on the Gene Expression Omnibus (GEO) database, we performed the transcriptional regulatory
22 networks (TRNs) to explain the mutual regulation relationship and the causal relationship between
23 transcription factors (TFs). We defined ten testicular cell types by their marker genes and found that
24 the proportion of Leydig cells (LCs) and macrophages (tMΦ) was significantly increased in iNOA
25 testis. We identified specific TFs included LHX9, KLF8, KLF4, ARID5B and RXRG in iNOA LCs.
26 In addition, we found specific TFs in iNOA tMΦ such as POU2F2, SPIB IRF5, CEBPA, ELK4 and
27 KLF6. All these identified TFs are strongly engaged in cellular fate, function and homeostasis of
28 microenvironment. Possibly, the changes in the activity of above identified TFs affect the function of
29 LCs and tMΦ and ultimately cause spermatogenesis failure. This study illustrate that these TFs play
30 important regulatory roles in the occurrence and development of NOA.