研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

集体迁移的增加与基底脊索动物中生殖系干细胞的竞争相关。

Increased collective migration correlates with germline stem cell competition in a basal chordate.

发表日期:2023
作者: Megan K Fentress, Anthony W De Tomaso
来源: Parasites & Vectors

摘要:

细胞竞争是一个比较祖细胞相对适应性的过程,产生获胜者,进一步促进发育,失败者被排除在外,并且可能是一种有助于个体适应性的通用质量控制过程。细胞竞争也会产生病理后果,并可能产生导致肿瘤进展的超级竞争细胞。我们正在研究群体海鞘(Botryllus schlosseri)种系再生过程中的细胞竞争。生殖系再生是由于生殖系干细胞 (GSC) 的存在而产生的,它具有独特的特性:竞争表型。当一个个体的 GSC 被移植到另一个个体时,供体细胞和受体细胞会竞争种系发育。通常,供体 GSC 会获胜,并完全取代受体的配子,这一过程称为生殖细胞寄生 (GCP)。 GCP 是一种遗传性状,获胜者和失败者的基因型可以在自然界中找到并在实验室中培养。然而,gcp 的分子和细胞机制尚不清楚。使用离体迁移测定,我们发现从获胜者基因型中分离出的 GSC 比失败者迁移得更快,并且在更大的簇中,并且簇大小与 Notch 配体 Jagged 的​​表达相关。簇大小和锯齿状表达都可以以基因型依赖的方式同时操纵:用肝细胞生长因子处理失败者 GSC 会增加锯齿状表达和簇大小,而 MAPK 途径的抑制剂会减少获胜者 GSC 中的锯齿状表达和簇大小。对移植有标记的获胜者和失败者 GSC 的个体进行的实时成像显示,它们迁移到生态位,有些是小簇,获胜者在生态位占有率方面具有轻微优势。总之,这表明 GSC 竞争的基础在于归巢能力和生态位占据的组合,并且可能通过 Notch 途径的差异利用来控制。版权所有:© 2023 Fentress, De Tomaso。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
Cell competition is a process that compares the relative fitness of progenitor cells, resulting in winners, which contribute further to development, and losers, which are excluded, and is likely a universal quality control process that contributes to the fitness of an individual. Cell competition also has pathological consequences, and can create super-competitor cells responsible for tumor progression. We are studying cell competition during germline regeneration in the colonial ascidian, Botryllus schlosseri. Germline regeneration is due to the presence of germline stem cells (GSCs) which have a unique property: a competitive phenotype. When GSCs from one individual are transplanted into another, the donor and recipient cells compete for germline development. Often the donor GSCs win, and completely replace the gametes of the recipient- a process called germ cell parasitism (gcp). gcp is a heritable trait, and winner and loser genotypes can be found in nature and reared in the lab. However, the molecular and cellular mechanisms underlying gcp are unknown. Using an ex vivo migration assay, we show that GSCs isolated from winner genotypes migrate faster and in larger clusters than losers, and that cluster size correlates with expression of the Notch ligand, Jagged. Both cluster size and jagged expression can be manipulated simultaneously in a genotype dependent manner: treatment of loser GSCs with hepatocyte growth factor increases both jagged expression and cluster size, while inhibitors of the MAPK pathway decrease jagged expression and cluster size in winner GSCs. Live imaging in individuals transplanted with labeled winner and loser GSCs reveal that they migrate to the niche, some as small clusters, with the winners having a slight advantage in niche occupancy. Together, this suggests that the basis of GSC competition resides in a combination in homing ability and niche occupancy, and may be controlled by differential utilization of the Notch pathway.Copyright: © 2023 Fentress, De Tomaso. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.