Article
Cell Biology
Fan Yang, Eoin C. Whelan, Xuebing Guan, Bingquan Deng, Shu Wang, Jiachen Sun, Mary R. Avarbock, Xin Wu, Ralph L. Brinster
Summary: Overexpression of Fgf9 in vivo results in arrested spermatogenesis and accumulation of undifferentiated spermatogonia; exposure of germ cell cultures to FGF9 leads to increased numbers of SSCs over time; inhibition of p38 MAPK phosphorylation negates the growth advantage provided by FGF9.
CELL PROLIFERATION
(2021)
Article
Cell Biology
Xiaomin Du, Siyu Wu, Yudong Wei, Xiuwei Yu, Fanglin Ma, Yuanxin Zhai, Donghui Yang, Mengfei Zhang, Wenqing Liu, Haijing Zhu, Jiang Wu, Mingzhi Liao, Na Li, Chunling Bai, Guangpeng Li, Jinlian Hua
Summary: The study identified a subset of spermatogonial stem cells in dairy goats with high PAX7 expression, indicating that PAX7 can maintain the self-renewal of these cells.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Cell Biology
Shreya Rajachandran, Xin Zhang, Qiqi Cao, Andre L. Caldeira-Brant, Xiangfan Zhang, Youngmin Song, Melanie Evans, Orhan Bukulmez, Edward J. Grow, Makoto Nagano, Kyle E. Orwig, Haiqi Chen
Summary: In this study, the molecular, cellular, and spatial composition of SSC niches was systematically dissected using spatial transcriptomics, computational analyses, and functional assays. The results showed that pleiotrophin regulates mouse SSC functions through syndecan receptors, and ephrin-A1 may be a niche factor that influences human SSC functions. Moreover, the spatial re-distribution of inflammation-related LR interactions was found to underlie diabetes-induced testicular injury. This study provides a systems approach to understanding the complex organization of the stem cell microenvironment in health and disease.
Article
Biochemistry & Molecular Biology
Jun Yu, Cong Shen, Meng Lin, Xia Chen, Xiuliang Dai, Zhiran Li, Yunhao Wu, Yangbo Fu, Jinxing Lv, Xiaoyan Huang, Bo Zheng, Fei Sun
Summary: In this study, we identified BMI1 as a key regulator of spermatogonial stem cell (SSC) maintenance. BMI1 represses target genes by increasing H2AK119ub and reducing H3K4me3 in SSCs. Additionally, BMI1 inhibition activates Wnt signaling and promotes nuclear translocation of beta-catenin in SSCs. Suppression of Wnt/beta-catenin signaling restores SSC maintenance in BMI1-deficient SSCs. Our findings not only reveal a novel mechanism for BMI1 in SSC maintenance, but also provide a potential strategy for treating male infertility.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Cell Biology
Chaoyue Zhong, Yuhao Tao, Meifeng Liu, Xi Wu, Yang Yang, Tong Wang, Zining Meng, Hongyan Xu, Xiaochun Liu
Summary: An SSC line derived from the adult testis of grouper was successfully established. These cells exhibited characteristics of SSCs and could be induced to express meiotic markers and produce sperm-like cells. The findings of this study have important implications for understanding the mechanisms of SSC self-renewal and differentiation, spermatogenesis, and sex reversal.
Article
Cell & Tissue Engineering
Shenae L. Cafe, David A. Skerrett-Byrne, Camila Salum De Oliveira, Brett Nixon, Melissa J. Oatley, Jon M. Oatley, Tessa Lord
Summary: The nucleosome remodeling protein CHD4 plays a key role in regulating SSC function, with its loss impairing SSC regenerative capacity. CHD4 affects gene expression in spermatogonia not only through its association with the remodeling complex NuRD but also via interaction with the GDNF-responsive transcription factor SALL4, influencing fate decisions and maintenance in the spermatogonial pool.
Review
Cell Biology
Bang-Hong Wei, Shuang-Li Hao, Wan-Xi Yang
Summary: This paper summarizes the niche and intrinsic factors involved in regulating self-renewal and proliferation of spermatogonial stem cells (SSCs), as well as their roles in SSC fate determination.
HISTOLOGY AND HISTOPATHOLOGY
(2022)
Article
Cell Biology
Seung-Jun Lee, Ka-Hwa Kim, Dong-Joon Lee, Pyunggang Kim, Jinah Park, Seong-Jin Kim, Han-Sung Jung
Summary: Spermatogonial stem cell (SSC) self-renewal is regulated by reciprocal interactions between Sertoli cells and SSCs in the testis. The study focused on the mechanism by which MAST4 in Sertoli cells transmits the signal and regulates SSCs, especially cell cycle regulation. The results demonstrate that MAST4 plays a pivotal role in maintaining the cell cycle of SSCs via the CDK2-PLZF interaction.
CELL PROLIFERATION
(2023)
Article
Genetics & Heredity
Himasadat Zaker, Mazdak Razi, Alireza Mahmoudian, Farhad Soltanalinejad
Summary: The study shows that testosterone stimulates the production of Gdnf in Sertoli cells, while Gdnf amplifies its receptor expression to affect the self-renewal of spermatogonial stem cells and spermatogenesis. Both testosterone and Gdnf can up-regulate the expression of Gdnf receptors at different concentrations.
Article
Multidisciplinary Sciences
Cheng Jin, Zhipeng Wang, Pengyu Li, Jielin Tang, Tao Jiao, Yiran Li, Jinhuan Ou, Dingfeng Zou, Mengzhen Li, Xinyu Mang, Jun Liu, Yanni Ma, Xiaolong Wu, Jie Shi, Shitao Chen, Manman He, Yan Lu, Ning Zhang, Shiying Miao, Fei Sun, Linfang Wang, Kai Li, Jia Yu, Wei Song
Summary: This study investigates the intercellular interactions between spermatogonial stem cell (SSC) and testicular niche in both adult mice and humans, uncovering the crucial role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in maintaining SSC homeostasis. The clinical relevance of specific paracrine factors in human fertility is also established.
Article
Cell Biology
Guoqing Yang, Yuqing He, Hao Yang
Summary: Recent research challenges the previous notion that spermatogonial stem cells (SSCs) are unipotent stem cells only capable of differentiating into spermatids, showing evidence that they can give rise to cell lineages of all three germ layers, with potential applications in regenerative medicine. However, the intrinsic regulation and strict control of SSC proliferation and stemness maintenance in a unique niche microenvironment remain unclear.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Cell Biology
Kun Tan, Hye-Won Song, Miles F. Wilkinson
Summary: The generation of mouse Spermatogonial Stem Cells (SSCs) is driven by a transcription factor (TF) cascade controlled by the homeobox protein, RHOX10. This cascade involves the differentiation of SSC precursors and the identification of RHOX10-regulated genes associated with SSC development. The study provides important insights into germ cell development and how transcription factor cascades are defined.
Article
Biochemistry & Molecular Biology
Susha K. Subash, Pradeep G. Kumar
Summary: Mammalian spermatogenesis is a complex process where spermatogonial stem cells develop into spermatozoa. The fate of these stem cells is determined by intrinsic and extracellular signals, with potential clinical applications in male infertility and germline modification.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2021)
Article
Multidisciplinary Sciences
Joachim Hanna, Flavio Beke, Louise M. O'Brien, Chrysa Kapeni, Hung-Chang Chen, Valentina Carbonaro, Alexander B. Kim, Kamal Kishore, Timon E. Adolph, Mikkel-Ole Skjoedt, Karsten Skjoedt, Marc de la Roche, Maike de la Roche
Summary: The study implicates Hedgehog signaling in Th17 polarization and intestinal immunopathology, suggesting the potential therapeutic use of Hedgehog inhibitors in the treatment of inflammatory bowel disease.
NATURE COMMUNICATIONS
(2022)
Review
Endocrinology & Metabolism
William W. Wright
Summary: This review focuses on the in vivo regulation of spermatogonial stem cells (SSCs) in adult testes by glial cell line-derived neurotrophic factor (GDNF). Through chemical-genetic approach, the inhibition of GDNF stimulation of SSCs was found to decrease replication and increase differentiation of SSCs, ultimately leading to the loss of all SSCs and resembling the condition of Sertoli cell-only (SCO) syndrome. Abnormally low expression of GDNF, FGF2, and FGF8 was observed in infertile human testes, although some SCO testes still contain SSCs. Restoration of GDNF signaling showed partial rebuilding of depleted SSC pool, suggesting GDNF as a potential therapy for men with SCO syndrome.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Bo Xu, Xiang Wei, Minjian Chen, Kaipeng Xie, Yuqing Zhang, Zhenyao Huang, Tianyu Dong, Weiyue Hu, Kun Zhou, Xiumei Han, Xin Wu, Yankai Xia
MOLECULAR MEDICINE REPORTS
(2019)
Article
Developmental Biology
Guihua Du, Xinrui Wang, Mengcheng Luo, Weiya Xu, Tao Zhou, Mei Wang, Luping Yu, Lufan Li, Li'e Cai, P. Jeremy Wang, John Zhong Li, Jon M. Oatley, Xin Wu
Article
Cell Biology
Mei Wang, Luping Yu, Shu Wang, Fan Yang, Min Wang, Lufan Li, Xin Wu
JOURNAL OF CELL SCIENCE
(2020)
Article
Genetics & Heredity
Chuncheng Lu, Yan Zhang, Yufeng Qin, Qiaoqiao Xu, Ran Zhou, Yiqiang Cui, Yunfei Zhu, Xin Zhang, Jintao Zhang, Xiang Wei, Min Wang, Bo Hang, Jian-Hua Mao, Antoine M. Snijders, Mingxi Liu, Zhibin Hu, Hongbing Shen, Zuomin Zhou, Xuejiang Guo, Xin Wu, Xinru Wang, Yankai Xia
Summary: This study identified four low-frequency variant genes associated with male infertility through X chromosome exome sequencing and functional experiments, providing new insights into the critical role of X-linked genes in spermatogenesis.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Reproductive Biology
Mi Yang, Bingquan Deng, Lei Geng, Lufan Li, Xin Wu
Article
Developmental Biology
Luping Yu, Huiru Zhang, Xuebing Guan, Dongdong Qin, Jian Zhou, Xin Wu
Summary: The study shows that the loss of Esrp1 leads to female infertility in mice, primarily affecting spindle organization, chromosome alignment, and oocyte meiosis. Single-cell RNA-seq analysis revealed 528 aberrant alternative splicing events associated with microtubule cytoskeletal organization.
Article
Reproductive Biology
Nilam Sinha, Eoin C. Whelan, John W. Tobias, Mary Avarbock, Darko Stefanovski, Ralph L. Brinster
Summary: Genes stimulated by retinoic acid 8 (Stra8) and transcription elongation regulator-1 like (Tcerg1l) are necessary in early-stage male germ cell differentiation induced by retinoic acid (RA). Stra8 is critical in modulating the responsiveness of undifferentiated spermatogonia to RA.
BIOLOGY OF REPRODUCTION
(2021)
Article
Developmental Biology
Guihua Du, Melissa J. Oatley, Nathan C. Law, Colton Robbins, Xin Wu, Jon M. Oatley
Summary: During development, the undifferentiated spermatogonial population in mammals plays a crucial role during a quiescence period, with disruptions in mitotic arrest leading to apoptosis in prospermatogonia and loss of germ cells. Single-cell RNA-sequencing analysis reveals that oxidative phosphorylation activity and meiotic initiation are affected in prospermatogonia without a normal quiescence period, suggesting that key programming layers are established during this period for proper fate determination and postnatal fitness.
Article
Cell Biology
Weiya Xu, Yiyun Zhang, Dongdong Qin, Yiqian Gui, Shu Wang, Guihua Du, Fan Yang, Lufan Li, Shuiqiao Yuan, Mei Wang, Xin Wu
Summary: TCFL5 plays an important role in mouse testes. Heterozygous Tcfl5(+/-) mice show reproductive abnormalities, and TCFL5 transcriptionally and post-transcriptionally regulates a set of genes involved in male germ cell development. Additionally, TCFL5 interacts with RNA-binding protein FXR1, which may regulate the transition and localization of TCFL5.
JOURNAL OF CELL SCIENCE
(2022)
Article
Cell Biology
Huaqin Yuan, Jiachen Sun, Shengnan Wang, Ziyi Xiang, Fan Yang, Yaping Yan, Yanchao Duan, Lufan Li, Xin Wu, Wei Si
Summary: This study characterized germ cells in macaque testes and successfully isolated spermatogenic cells with high purity. Autologous cell transplantation in macaque testes was mimicked under ultrasonographic guidance. Although SSC propagation in vitro was not significant, monkey testicular germ cells with stem cell characteristics were maintained.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Eoin C. Whelan, Fan Yang, Mary R. Avarbock, Megan C. Sullivan, Daniel P. Beiting, Ralph L. Brinster
Summary: Cancer treatment may cause infertility in prepubertal boys, and the current strategy for preserving fertility is cryopreservation of testicular biopsy. However, long-term freezing can impact the success of transplantation and spermatogenesis, which must be considered in therapeutic applications.
Article
Cell Biology
Chao Li, Yuming Feng, Zhenxin Fu, Junjie Deng, Yue Gu, Hanben Wang, Xin Wu, Zhengyun Huang, Yichen Zhu, Zhiwei Liu, Moli Huang, Tao Wang, Shijun Hu, Bing Yao, Yizhun Zeng, Chengji J. Zhou, Steve D. M. Brown, Yi Liu, Antonio Vidal-Puig, Yingying Dong, Ying Xu
Summary: This study discovered the crucial role of the CT47 gene family in human-specific spermatogenesis. CT47 inhibits spermatogenesis by stabilizing PRMT5 and interacting with its accumulation in the nucleus. Testosterone decreases the nuclear concentration of CT47/PRMT5 and promotes spermatocyte progression. Loss of CT47 in human embryonic stem cells prevents the testosterone-induced increase in haploid cells.
CELL DEATH DISCOVERY
(2022)
Article
Medicine, Research & Experimental
Xu Yang, Guilin Li, Yuhua Tian, Xin Wang, Jiuzhi Xu, Ruiqi Liu, Min Deng, Chunlei Shao, Yuwei Pan, Xi Wu, Mengzhen Li, Chaowei Zhang, Rui Liu, Jun Qin, Chen Zhang, Zhanju Liu, Xin Wu, Maksim Plikus, Christopher J. Lengner, Zongheng Zheng, Cong Lv, Zhengquan Yu
Summary: The E2F3-MEX3A-KLF4 axis plays a crucial role in the self-renewal and differentiation of cancer stem cells, suggesting it as a potential druggable target for cancer differentiation therapy.
Article
Cell Biology
Fan Yang, Eoin C. Whelan, Xuebing Guan, Bingquan Deng, Shu Wang, Jiachen Sun, Mary R. Avarbock, Xin Wu, Ralph L. Brinster
Summary: Overexpression of Fgf9 in vivo results in arrested spermatogenesis and accumulation of undifferentiated spermatogonia; exposure of germ cell cultures to FGF9 leads to increased numbers of SSCs over time; inhibition of p38 MAPK phosphorylation negates the growth advantage provided by FGF9.
CELL PROLIFERATION
(2021)