Dissecting the spermatogonial stem cell niche using spatial transcriptomics
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
Affiliations
Shreya Rajachandran
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Xin Zhang
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Qiqi Cao
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Andre L. Caldeira-Brant
Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Xiangfan Zhang
Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
Youngmin Song
Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
Melanie Evans
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Orhan Bukulmez
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Edward J. Grow
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Makoto Nagano
Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
Kyle E. Orwig
Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Haiqi Chen
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Corresponding author
Summary: Spermatogonial stem cells (SSCs) in the testis support the lifelong production of sperm. SSCs reside within specialized microenvironments called “niches,” which are essential for SSC self-renewal and differentiation. However, our understanding of the molecular and cellular interactions between SSCs and niches remains incomplete. Here, we combine spatial transcriptomics, computational analyses, and functional assays to systematically dissect the molecular, cellular, and spatial composition of SSC niches. This allows us to spatially map the ligand-receptor (LR) interaction landscape in both mouse and human testes. Our data demonstrate that pleiotrophin regulates mouse SSC functions through syndecan receptors. We also identify ephrin-A1 as a potential niche factor that influences human SSC functions. Furthermore, we show that the spatial re-distribution of inflammation-related LR interactions underlies diabetes-induced testicular injury. Together, our study demonstrates a systems approach to dissect the complex organization of the stem cell microenvironment in health and disease.
