Frontiers in Cell and Developmental Biology (Aug 2021)
TCF3 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cells by Targeting PODXL
- Dai Zhou,
- Dai Zhou,
- Dai Zhou,
- Dai Zhou,
- Dai Zhou,
- Jingyu Fan,
- Zhizhong Liu,
- Zhizhong Liu,
- Ruiling Tang,
- Ruiling Tang,
- Xingming Wang,
- Xingming Wang,
- Hao Bo,
- Hao Bo,
- Fang Zhu,
- Fang Zhu,
- Xueheng Zhao,
- Xueheng Zhao,
- Zenghui Huang,
- Zenghui Huang,
- Liu Xing,
- Liu Xing,
- Ke Tao,
- Ke Tao,
- Ke Tao,
- Han Zhang,
- Han Zhang,
- Hongchuan Nie,
- Hongchuan Nie,
- Huan Zhang,
- Huan Zhang,
- Wenbing Zhu,
- Wenbing Zhu,
- Zuping He,
- Liqing Fan,
- Liqing Fan,
- Liqing Fan,
- Liqing Fan
Affiliations
- Dai Zhou
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Dai Zhou
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Dai Zhou
- College of Life Sciences, Hunan Normal University, Changsha, China
- Dai Zhou
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- Dai Zhou
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China
- Jingyu Fan
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, United States
- Zhizhong Liu
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Zhizhong Liu
- Department of Urology, Hunan Cancer Hospital, Changsha, China
- Ruiling Tang
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Ruiling Tang
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Xingming Wang
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Xingming Wang
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Hao Bo
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Hao Bo
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Fang Zhu
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Fang Zhu
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Xueheng Zhao
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Xueheng Zhao
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Zenghui Huang
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Zenghui Huang
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Liu Xing
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Liu Xing
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Ke Tao
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Ke Tao
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Ke Tao
- The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University School of Medicine, Changsha, China
- Han Zhang
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Han Zhang
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Hongchuan Nie
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Hongchuan Nie
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Huan Zhang
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Huan Zhang
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Wenbing Zhu
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Wenbing Zhu
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Zuping He
- The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University School of Medicine, Changsha, China
- Liqing Fan
- Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, China
- Liqing Fan
- Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- Liqing Fan
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- Liqing Fan
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China
- DOI
- https://doi.org/10.3389/fcell.2021.695545
- Journal volume & issue
-
Vol. 9
Abstract
Spermatogonial stem cells (SSCs) are the initial cells for the spermatogenesis. Although much progress has been made on uncovering a number of modulators for the SSC fate decisions in rodents, the genes mediating human SSCs remain largely unclear. Here we report, for the first time, that TCF3, a member of the basic helix-loop-helix family of transcriptional modulator proteins, can stimulate proliferation and suppress the apoptosis of human SSCs through targeting podocalyxin-like protein (PODXL). TCF3 was expressed primarily in GFRA1-positive spermatogonia, and EGF (epidermal growth factor) elevated TCF3 expression level. Notably, TCF3 enhanced the growth and DNA synthesis of human SSCs, whereas it repressed the apoptosis of human SSCs. RNA sequencing and chromatin immunoprecipitation (ChIP) assays revealed that TCF3 protein regulated the transcription of several genes, including WNT2B, TGFB3, CCN4, MEGF6, and PODXL, while PODXL silencing compromised the stem cell activity of SSCs. Moreover, the level of TCF3 protein was remarkably lower in patients with spermatogenesis failure when compared to individuals with obstructive azoospermia with normal spermatogenesis. Collectively, these results implicate that TCF3 modulates human SSC proliferation and apoptosis through PODXL. This study is of great significance since it would provide a novel molecular mechanism underlying the fate determinations of human SSCs and it could offer new targets for gene therapy of male infertility.
Keywords