NF-YB Regulates Spermatogonial Stem Cell Self-Renewal and Proliferation in the Planarian Schmidtea mediterranea.
NF-YB Regulates Spermatogonial Stem Cell Self-Renewal and Proliferation in the Planarian Schmidtea mediterranea.
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DOI：
10.1371/journal.pgen.1006109
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发表时间：
2016-06
期刊：
影响因子：
4.5
通讯作者：
Newmark PA
中科院分区：
文献类型：
--
作者：
Iyer H;Collins JJ 3rd;Newmark PA
配子是遗传信息的来源和载体，对所有有性生殖生物的繁殖至关重要。雄性配子来源于称为精原干细胞（SSC）的祖细胞群。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的精子。这种平衡的破坏可导致SSC过度增殖，引起肿瘤发生，或可导致异常分化，导致不育。关于精原干细胞如何实现自我更新和分化之间的良好平衡，人们知之甚少，而这是其显著的产量和发育潜力所必需的。为了了解SSC维护的机制，我们研究了Planarian同源核因子Y-B（NF-YB），这是维持早期Planarian雄性生殖细胞所必需的。在这里，我们证明了NF-YB在涡虫SSCs的自我更新和增殖中起作用，但在它们的特化或分化中不起作用。此外，我们还描述了曼氏血吸虫NF-Y复合体的成员，曼氏血吸虫是一种与自由生活的真涡虫相关的寄生扁虫。我们发现NF-YB在调节雄性生殖细胞增殖中的功能在染色体中是保守的。这一发现尤其重要，因为生殖力是S. mansoni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意义。有性繁殖的生物体需要配子精子和卵子来维持生命并在两代人之间传递遗传信息。雄性配子（精子）来自一群专门的干细胞，称为精原干细胞（SSC）。确定参与SSC维持的因素具有重要的生物医学意义，包括破译睾丸肿瘤的病因和优化生育治疗。在这里，我们表明，一个男性生殖细胞特异性同源物的普遍存在的核因子-Y家族的转录因子，NF-YB，是必需的自我更新和增殖的精原细胞在淡水涡虫，Schmidtea mediterranea。此外，我们将研究扩展到寄生扁虫曼氏血吸虫（Schistosoma mansoni），它是主要被忽视的热带疾病血吸虫的病原体，也是自由生活的真涡虫的进化近亲。我们发现，有一个损失的增殖细胞在睾丸中的寄生虫时，NF-Y的成分被抑制。这一观察结果是有意义的，因为S.曼氏病是与血吸虫病相关的发病率的主要原因。总之，我们的研究结果建立NF-YB作为一个重要的调节SSC的维护，并可能开辟途径，打击血吸虫病。
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. 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.