Cell lineage analysis of the mammalian female germline.
Cell lineage analysis of the mammalian female germline.
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DOI：
10.1371/journal.pgen.1002477
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Shapiro E
中科院分区：
文献类型：
--
作者：
Reizel Y;Itzkovitz S;Adar R;Elbaz J;Jinich A;Chapal-Ilani N;Maruvka YE;Nevo N;Marx Z;Horovitz I;Wasserstrom A;Mayo A;Shur I;Benayahu D;Skorecki K;Segal E;Dekel N;Shapiro E
胚胎和产后发育的基本方面，包括哺乳动物雌性种系的维持，在很大程度上是未知的。在这里，我们采用回顾性的、基于系统发育的方法，利用微卫星中积累的体细胞突变重建细胞谱系树，以研究小鼠的雌性种系动力学。重建的细胞谱系树可用于估计不同细胞类型之间的谱系关系，以及细胞深度（自受精卵以来的细胞分裂次数）。我们发现，在重建的小鼠细胞谱系树中，年轻和年老小鼠的卵母细胞形成与造血干细胞和间充质干细胞分开的簇，表明这些群体属于不同的谱系。此外，虽然从不同卵泡中采集的卵丘细胞明显聚集在重建的树上，但来自左右卵巢的卵母细胞却没有，这表明它们的祖细胞池是混合的。我们还观察到卵母细胞深度随着小鼠年龄的增长而增加，这可以通过深度引导的排卵卵母细胞选择或产后更新来解释。总的来说，我们的研究揭示了女性种系保存和发育的实质性新颖方面。哺乳动物雌性种系发育在胚胎发生期间和整个成年期的许多方面要么是未知的，要么是有争议的。在这项研究中，我们应用了一种新方法，利用小鼠生命期间在卵母细胞和其他细胞中积累的微卫星突变来重建细胞谱系树，这些微卫星突变从年轻和年老的小鼠中取样。对重建的细胞谱系树的分析表明，卵母细胞与骨髓来源的细胞分开聚集，来自不同卵巢的卵母细胞具有共同的祖细胞，并且卵母细胞深度（自受精卵以来的细胞分裂次数）随着小鼠年龄的增长而显着增加。
Fundamental aspects of embryonic and post-natal development, including maintenance of the mammalian female germline, are largely unknown. Here we employ a retrospective, phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites, to study female germline dynamics in mice. Reconstructed cell lineage trees can be used to estimate lineage relationships between different cell types, as well as cell depth (number of cell divisions since the zygote). We show that, in the reconstructed mouse cell lineage trees, oocytes form clusters that are separate from hematopoietic and mesenchymal stem cells, both in young and old mice, indicating that these populations belong to distinct lineages. Furthermore, while cumulus cells sampled from different ovarian follicles are distinctly clustered on the reconstructed trees, oocytes from the left and right ovaries are not, suggesting a mixing of their progenitor pools. We also observed an increase in oocyte depth with mouse age, which can be explained either by depth-guided selection of oocytes for ovulation or by post-natal renewal. Overall, our study sheds light on substantial novel aspects of female germline preservation and development. Many aspects of mammalian female germline development during embryogenesis and throughout adulthood are either unknown or under debate. In this study we applied a novel method for the reconstruction of cell lineage trees utilizing microsatellite mutations, accumulated during mouse life, in oocytes and other cells, sampled from young and old mice. Analysis of the reconstructed cell lineage trees shows that oocytes are clustered separately from bone-marrow derived cells, that oocytes from different ovaries share common progenitors, and that oocyte depth (number of cell divisions since the zygote) increases significantly with mouse age.
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