NF-YB Regulates Spermatogonial Stem Cell Self-Renewal and Proliferation in the Planarian Schmidtea mediterranea

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.配子是遗传信息的来源与载体，对所有有性繁殖生物的繁衍至关重要。雄性配子源自一类被称为精原干细胞（spermatogonial stem cells, SSCs）的祖干细胞群。SSCs通过两大核心过程的协同调控产生雄性配子：一是自我更新以产生更多SSCs，二是分化为成熟精子。这种平衡一旦被打破，要么会导致SSCs过度增殖引发肿瘤发生，要么会造成异常分化，进而引发不育。目前学界对SSCs如何实现自我更新与分化间的精细平衡知之甚少，而这种平衡正是其卓越的产出能力与发育潜能所必需的。为阐明SSC维持的机制，我们研究了涡虫的核因子Y-B（Nuclear Factor Y-B, NF-YB）同源基因，该基因对于涡虫早期雄性生殖细胞的维持是必需的。本研究证实，NF-YB在涡虫SSCs的自我更新与增殖过程中发挥作用，但不参与其特化或分化进程。此外，我们还对与自由生活涡虫亲缘关系较近的寄生扁形动物曼氏血吸虫（Schistosoma mansoni）体内的NF-Y复合体成员进行了表征。研究发现，NF-YB调控雄性生殖细胞增殖的功能在血吸虫中是保守的。这一发现具有重要意义，因为曼氏血吸虫的致病机制正是源于其繁殖力。我们的研究结果有助于厘清SSCs自我更新与分化间的复杂关联，同时也可能为理解并控制血吸虫病提供新思路。