Iyer Harini, Collins James J, Newmark Phillip A
Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
PLoS Genet. 2016 Jun 15;12(6):e1006109. doi: 10.1371/journal.pgen.1006109. eCollection 2016 Jun.
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和载体，对于所有有性生殖生物的繁殖至关重要。雄性配子源自一种称为精原干细胞（SSCs）的祖干细胞群体。精原干细胞通过两个基本过程的协调产生雄性配子：自我更新以产生更多的精原干细胞，以及分化以产生成熟精子。这种平衡的破坏会导致精原干细胞过度增殖，引发肿瘤发生，或者导致异常分化，导致不育。关于精原干细胞如何在自我更新和分化之间实现精细平衡，人们知之甚少，而这种平衡对于它们显著的产出和发育潜力是必要的。为了理解精原干细胞维持的机制，我们研究了核因子Y-B（NF-YB）的涡虫同源物，它是早期涡虫雄性生殖细胞维持所必需的。在这里，我们证明NF-YB在涡虫精原干细胞的自我更新和增殖中起作用，但在其特化或分化中不起作用。此外，我们对曼氏血吸虫（一种与自由生活的涡虫相关的寄生扁虫）中NF-Y复合物的成员进行了表征。我们发现NF-YB在调节雄性生殖细胞增殖中的功能在血吸虫中是保守的。这一发现尤为重要，因为繁殖力是曼氏血吸虫发病机制的原因。我们的发现有助于阐明精原干细胞自我更新和分化之间的复杂关系，也可能对理解和控制血吸虫病有启示。
