巨细胞激活导致斑马鱼的卵巢衰竭和男性化
Paloma Bravo1, Yulong Liu2, Bruce W Draper2
1Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Science advances
|November 22, 2023
概括
骨形态遗传蛋白15 (BMP15) 突变导致卵巢衰竭. 在斑马鱼中,Bmp15损失激活了巨细胞,导致卵巢衰竭和性别逆转,揭示了一个新的生殖线-soma信号轴.
科学领域:
- 生殖生物学 生殖生物学
- 发育生物学是发展生物学.
- 免疫学 免疫学 免疫学
背景情况:
- 骨形态遗传蛋白15 (BMP15) 对脊椎动物的卵巢功能至关重要.
- 在BMP15中发生的突变与人类的过早卵巢衰竭有关.
- 与BMP15相关的卵巢衰竭的细胞机制和免疫参与仍然不清楚.
研究的目的:
- 阐明由BMP15突变引起的卵巢衰竭背后的细胞机制.
- 研究免疫细胞,特别是巨细胞在与BMP15相关的卵巢功能障碍中的作用.
- 为了确定参与卵巢维护和失败的信号通路.
主要方法:
- 使用斑马鱼作为模型生物来研究卵巢衰竭和性别逆转.
- 采用了遗传分析,包括Bmp15的生殖线损失和巨细胞的遗传切除.
- 进行单细胞RNA测序以识别关键细胞参与者和信号分子.
主要成果:
- 建立了巨细胞激活和卵巢衰竭之间的因果关系,导致斑马鱼的性别逆转.
- 鉴定了一种由Bmp15损失引发的生殖线-soma信号轴,该轴激活了巨细胞.
- 证明表达巨激活配体的卵巢体细胞调解卵巢衰竭和性别逆转;巨切除或阻断特定的配体 (Il34,Csf1a) 防止卵细胞损失和性别逆转.
结论:
- 斑马鱼的卵巢衰竭和雌雄性逆转是由一个由Bmp15启动的生殖线-soma信号轴驱动的,该轴激活了巨细胞.
- 卵巢体细胞通过保存的巨细胞激活配体在调解这个过程中发挥着关键作用.
- 这项研究提供了对卵细胞和卵巢维护途径的洞察,并确定了保护女性生育能力的潜在治疗点.
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