Ning Wang, Ph.D.
Molecular and Integrative Physiology
Brief Overview of Wang Lab Research
Male fertility relies on a rare population of spermatogonial stem cells (SSCs) in testes. In mice, SSCs, making up only ~0.03% of all germ cells, produce ~40 million sperm per gram of tissue per day by way of mitosis and meiosis. Proper maintenance of this small pool of SSCs is essential to sustain lifelong production of sperm. We have established a transgenic mouse line, in which the Stra8 promoter, whose activation is probably one of the earliest events during GSC differentiation of both sexes, drives GFP reporter expression (Stra8-GFP). We recently reported that, by using cell surface markers for undifferentiated and differentiating spermatogonia in Stra8-GFP mice, we are able to separate spermatogonia into six populations at consecutive differentiation stages (Figure 1; Xiong et al, Cell Cycle, 2015).
Thus, we are using this unique system to: 1) Characterize novel phenotypical markers of the primitive spermatogonial stem cells; 2) Investigate the mechanisms governing stem cell maintenance and differentiation.
In addition to SSCs, we are currently investigating how spermatogonial cells commit meiosis. Meiotic initiation is a key feature of sexual reproduction that launches an intricate chromosomal program involving DNA double strand breaks (DSBs), homolog pairing, cohesion, synapsis, and recombination. Vertebrate gene Stra8 is an essential gatekeeper of meiotic initiation. However, the molecular role of STRA8 and its target genes remain elusive. Using mouse spermatogenesis as a model, we recently reported that STRA8 suppresses autophagy by repressing the transcription of a nuclear hormone receptor gene Nr1d1, and in turn, silencing the expression of Ulk1, a gene essential for autophagy initiation (Figure 2; Ferder et al, PLoS Genetics, 2018). Given that autophagy is critical for protein and cellular organelle recycling and for preventing genomic instability, our study suggests that this newly demonstrated function of STRA8, as a suppressor of autophagy, may be an important mechanistic feature of its role in meiotic initiation. Currently, we are using a combination of molecular, cellular, and genetic approaches to investigate autophagic regulation of meiotic initiation during germline development.