Branched germline cysts and female-specific cyst fragmentation facilitate oocyte determination in mice.

Branched germline cysts and female-specific cyst fragmentation facilitate oocyte determination in mice.
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DOI:
10.1073/pnas.2219683120
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发表时间:
2023-05-16
影响因子:
11.1
通讯作者:
Lei, Lei
Lei, Lei
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ikami, Kanako;Shoffner-Beck, Suzanne;Weh, Malgorzata Tyczynska;Schnell, Santiago;Yoshida, Shosei;Miranda, Edgar Andres Diaz;Ko, Sooah;Lei, Lei

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在雌性哺乳动物中,胎儿卵巢中大规模的生殖细胞死亡导致只有一小部分生殖细胞成为卵母细胞。在这项研究中,我们发现小鼠胚胎生殖细胞形成分支囊肿结构,其中约17%的细胞由三个或四个细胞间桥连接。在雌性包囊中,这些生殖细胞优先通过从姐妹生殖细胞收集细胞内容物而免于细胞死亡而成为卵母细胞。这些结果提示了在胎儿卵巢发育过程中,维持成年卵巢功能的卵母细胞是如何决定的。与雌性生殖细胞不同,雄性生殖细胞在每个分支囊肿内具有相同的细胞命运。在小鼠配子发生过程中,来自同一祖细胞的生殖细胞通过细胞间桥连接,形成生殖细胞包囊,其中雌性和雄性生殖细胞分别发生不对称或对称的细胞命运。在这里,我们已经确定了分支囊肿结构的小鼠,并研究它们的形成和卵母细胞决定的功能。在胎儿女性囊肿中,16.8%的生殖细胞由三个或四个桥连接,即分支生殖细胞。这些生殖细胞优先受到保护,免于细胞死亡和包囊破碎,并积累来自姐妹生殖细胞的细胞质和细胞器,成为初级卵母细胞。囊肿结构的变化和差异细胞体积之间的囊肿生殖细胞表明,细胞质运输在生殖细胞系囊肿进行定向的方式,其中细胞内容物首先在外周生殖细胞之间局部运输,并进一步丰富分支生殖细胞,一个过程导致选择性生殖细胞损失囊肿。囊肿破裂广泛发生在女性囊肿,但不发生在男性囊肿。胎儿和成人睾丸中的男性囊肿具有分支的囊肿结构,生殖细胞之间没有不同的细胞命运。在胎儿囊肿形成期间,生殖细胞之间的E-钙粘蛋白(E-cad)连接定位细胞间桥以形成分支囊肿。在E-cad耗尽囊肿中中断的连接形成导致分支囊肿中的比率改变。生殖细胞特异性E-cad敲除导致初级卵母细胞数量和卵母细胞大小减少。这些发现揭示了卵母细胞的命运是如何决定在小鼠生殖细胞囊肿。
In mammalian females, a large-scale germ cell death in fetal ovaries results in only a small proportion of germ cells becoming oocytes. In this study, we identified that mouse fetal germ cells form branched cyst structures where ~17% of the cells are connected by three or four intercellular bridges. In female cysts, these germ cells are preferentially protected from cell death to become oocytes through collecting cellular content from sister germ cells. These results suggest a mechanism on how the oocytes available for sustaining adult ovarian function are determined during fetal ovary development. Unlike female germ cells, male germ cells share the same cell fate within each branched cyst. During mouse gametogenesis, germ cells derived from the same progenitor are connected via intercellular bridges forming germline cysts, within which asymmetrical or symmetrical cell fate occurs in female and male germ cells, respectively. Here, we have identified branched cyst structures in mice, and investigated their formation and function in oocyte determination. In fetal female cysts, 16.8% of the germ cells are connected by three or four bridges, namely branching germ cells. These germ cells are preferentially protected from cell death and cyst fragmentation and accumulate cytoplasm and organelles from sister germ cells to become primary oocytes. Changes in cyst structure and differential cell volumes among cyst germ cells suggest that cytoplasmic transport in germline cysts is conducted in a directional manner, in which cellular content is first transported locally between peripheral germ cells and further enriched in branching germ cells, a process causing selective germ cell loss in cysts. Cyst fragmentation occurs extensively in female cysts, but not in male cysts. Male cysts in fetal and adult testes have branched cyst structures, without differential cell fates between germ cells. During fetal cyst formation, E-cadherin (E-cad) junctions between germ cells position intercellular bridges to form branched cysts. Disrupted junction formation in E-cad-depleted cysts led to an altered ratio in branched cysts. Germ cell-specific E-cad knockout resulted in reductions in primary oocyte number and oocyte size. These findings shed light on how oocyte fate is determined within mouse germline cysts.
DOI: 10.1371/journal.pone.0012473
发表时间: 2010-08-31
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影响因子: 3.7
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发表时间: 2002-07-01
影响因子: 2.6
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发表时间: 2001-12-01
期刊: Medical Electron Microscopy
影响因子: --
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