在人类,奶牛和老鼠胚胎中启动保存的皮计划
Claudia Gerri1, Afshan McCarthy1, Gregorio Alanis-Lobato1
1Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, London, UK.
Nature
|September 24, 2020
概括
在人类,奶牛和老鼠胚胎中,一个保存的分子级联启动了托菲克多德的分离. 抑制非典型的蛋白激酶C (aPKC) 干扰了TE的启动,显示了哺乳动物早期的进化保存.
科学领域:
- 发育生物学
- 比较胚胎学
- 细胞生物学
背景情况:
- 哺乳动物的植入前发育涉及早期的细胞特异化,外部细胞形成体 (TE),内部细胞形成内部细胞质量.
- 对于理解这一过程,小鼠模型是主要的,但最近的研究表明人类和牛的变化.
- 识别保存机制对于理解进化发育生物学至关重要.
研究的目的:
- 在哺乳动物早期发育过程中研究调节体分离的分子机制的进化性保存.
- 确定在小鼠中启动 TE 规范的分子级联是否保留在人类和牛胚胎中.
- 阐明非典型蛋白激酶C (aPKC) 和河马信号在跨物种TE启动中的作用.
主要方法:
- 在人,牛和小鼠胚胎的基因表达的比较分析.
- 研究细胞极性和关键信号分子的局部化 (aPKC,Hippo通路效应器,GATA3).
- 使用Trim-Away对aPKC和蛋白质耗尽的药理抑制,以评估对TE启动的功能影响.
主要成果:
- 在人类,奶牛和老鼠胚胎中发现了启动TE分离的保存分子级联.
- 在毛囊阶段的外细胞表现出基极性,具有特定的aPKC和核Hippo通路效应者的定位.
- 抑制aPKC显著损害了TE的启动,突出显示了它在这个过程中的关键作用.
- 与TE相关的因子如GATA3的表达受到限制,这表明TE计划的启动.
结论:
- 类似的分子机制在人类,牛和老鼠胚胎中启动了托菲克托德 (TE) 规范,这表明进化保护.
- 基细胞极性和非典型的蛋白激酶C (aPKC) 途径对于启动TE分离至关重要.
- 这项研究提供了有关哺乳动物发育早期谱系规范的有价值的见解.
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