Gametes are the source and carrier of genetic information, essential for the propagation of all sexually reproducing organisms. Male gametes are derived from a progenitor stem cell population called spermatogonial stem cells (SSCs). SSCs give rise to male gametes through the coordination of two essential processes: self-renewal to produce more SSCs, and differentiation to produce mature sperm. Disruption of this equilibrium can lead to excessive proliferation of SSCs, causing tumorigenesis, or can result in aberrant differentiation, leading to infertility. Little is known about how SSCs achieve the fine balance between self-renewal and differentiation, which is necessary for their remarkable output and developmental potential. To understand the mechanisms of SSC maintenance, we examine the planarian homolog of Nuclear Factor Y-B (NF-YB), which is required for the maintenance of early planarian male germ cells. Here, we demonstrate that NF-YB plays a role in the self-renewal and proliferation of planarian SSCs, but not in their specification or differentiation. Furthermore, we characterize members of the NF-Y complex in Schistosoma mansoni , a parasitic flatworm related to the free-living planarian. We find that the function of NF-YB in regulating male germ cell proliferation is conserved in schistosomes. This finding is especially significant because fecundity is the cause of pathogenesis of S . mansoni . Our findings can help elucidate the complex relationship between self-renewal and differentiation of SSCs, and may also have implications for understanding and controlling schistosomiasis. Author Summary Sexually reproducing organisms require gametes–sperm and eggs–for the perpetuation of life and transmission of genetic information between generations. Male gametes (sperm) arise from a dedicated population of stem cells known as spermatogonial stem cells (SSCs). Identification of factors involved in SSC maintenance has important biomedical implications, including deciphering the etiology of testicular tumors and optimizing fertility treatments. Here we show that a male germ cell-specific homolog of the ubiquitous Nuclear Factor-Y family of transcription factors, NF-YB, is required for the self-renewal and proliferation of SSCs in the freshwater planarian, Schmidtea mediterranea . Additionally, we extend our study to the parasitic flatworm Schistosoma mansoni , the causative agent of the major neglected tropical disease schistosomiasis and evolutionary cousin of the free-living planarian. We find that there is a loss of proliferating cells in the testes of the parasite when schistosome NF-Y components are inhibited. This observation is significant since the reproductive output of S . mansoni is the primary cause of the morbidity associated with schistosomiasis. Together, our results establish NF-YB as an important regulator of SSC maintenance, and may open avenues for combating schistosomiasis.
【초록키워드】 stem cells, Tumor, Pathogenesis, Transmission, cells, morbidity, male, Sperm, etiology, differentiation, coordination, disease, mechanism, infertility, Propagation, Schistosomiasis, Disruption, SSC, identification, cell proliferation, tumors, maintenance, proliferation, stem cell, life, lead, balance, transcription factors, open, causative agent, germ cell, Schistosoma mansoni, tropical disease, germ cells, observation, Factor, Organisms, Implications, tumorigenesis, complex, help, organism, testes, genetic information, component, parasite, carrier, fecundity, homolog, cell population, implication, tropical, Cell, combating, conserved, involved, required, inhibited, reproductive, developmental, Gamete, schistosome, 【제목키워드】 stem cell, STEM, Planarian,