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METTL3 塑造了 m6A 表谱学景观,以成功地实现人类的胎盘形成

Ram Parikshan Kumar^1,2, Rajnish Kumar¹, Avishek Ganguly¹

¹Department of Pathology & Laboratory Medicine, University of Kansas Medical Center Kansas City, KS 66160, USA.

bioRxiv : the preprint server for biology

|July 19, 2024

概括

甲基转移酶类3 (METTL3) 对于人类的胎盘形成至关重要. 它在 trofhoblast 细胞中的平衡功能对妊娠成功至关重要,调节细胞更新和分化.

科学领域:

生殖生物学生殖生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
细胞生物学细胞生物学

背景情况:

甲基转移酶类3 (METTL3) 对于哺乳动物的发育至关重要.
对于METTL3在人类胎盘中的作用基本上是未知的.
RNA m6A甲基化是一个关键的表体转录基因修饰.

研究的目的:

调查METTL3在人类胎位中的作用.
确定METTL3失调对怀孕结果的影响.
阐明METTL3影响热囊细胞功能的分子机制.

主要方法:

对人类胎盘组织中METTL3表达的分析,这些胎盘组织来自具有不良后果的怀孕.
在人类热细胞干细胞 (TSC) 中的功能丧失和功能增强研究.
全球RNA m6A分析和RNA结合分析.
条件删除的METTL3在老鼠热细胞的祖先.

主要成果:

热囊细胞中METTL3的平衡对于人类成功的胎盘形成至关重要.
热囊细胞前代体中METTL3的损失与重复的妊娠损失和早产有关.
在胎儿生长限制 (FGR) 中,METTL3被上调.
METTL3对于TSC的自我更新和分化为外性热囊细胞 (EVTs) 是必不可少的.
失去METTL3有助于同胞细胞 (STB) 的发育.
METTL3调节m6A修饰关键的热囊细胞调节器mRNAs (例如,GATA2,GATA3,TEAD1).
在老鼠热细胞的祖先中,METTL3的删除阻止了自我更新.
METTL3 在热囊细胞前代体中起到保护性表体转录基因调节者的作用.

结论:

在人体胎盘中,METTL3发挥着关键的,保存的作用.
METTL3 调节了 trofhoblast 先生的自我更新和分化命运.
对METTL3的调节失调有助于妊娠的不良结果.

关键词:

埃克斯特拉维卢斯热囊细胞.在METTL3中,METTL3是METTL3的第一个类型.N6 - 甲基氨酸 (m6A) 的使用.胎盘胎盘胎盘胎盘在RNA中切割和运行.综合性类细胞.副本转录组 (epitranscriptome) 是一个副本转录组 (epitranscriptome).热囊细胞干细胞的干细胞

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