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一个修改调节了人体精子干细胞分化中的L1逆转移体在体外和体内的体外分化和体外分化

Zili Li^1,2, Fang Fang³, Mohammad Ishraq Zafar⁴

¹Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.

Cellular and molecular life sciences : CMLS

|February 16, 2024

概括

N6-甲基-腺素 (m6A) 修改对于人类生殖线发育中的基因组稳定性至关重要. 它限制了称为LINE-1 (L1) 逆转移体的移动遗传元素,防止它们有害的插入,并支持干细胞分化.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
基因组学就是基因组学.
发展生物学发展生物学

背景情况:

生殖系中的基因组完整性对于哺乳动物的发育至关重要.
长间隔的元素类型1 (LINE-1,L1) 逆转移子威胁到基因组的稳定性.
在L1逆转移和生殖线发育中N6-甲基-腺素 (m6A) 的作用基本上是未知的.

研究的目的:

为了研究m6的功能,在人类生殖线发育过程中调节L1逆转移素的修饰.
确定METTL3和YTHDF2在人类精子干细胞 (hSSC) 诱导和L1逆转换中的作用.

主要方法:

在人类胚胎干细胞 (hESCs) 中敲除m6A甲基转移酶METTL3或m6A读者YTHDF2.
在体外分析L1逆转换率和hSSC差异化效率.
检测m⁶A对L1逆转移体的修饰,并研究降解途径.
对L1逆转移素RNA和METTL3表达在患有亚精子症的患者的精液血中的分析.

主要成果:

METTL3和YTHDF2对于诱导hSSCs从hESCs至关重要.
失去METTL3或YTHDF2会增加L1的逆转换,并损害hSSC的分化.
通过自,YTHDF2调解了m6A修饰的L1mRNA的降解,抑制了逆转换.
在中介性停止的亚子精患者中观察到升高的L1RNA和降低的METTL3表达.

结论:

一个修改通过限制L1逆转换来作为人类生殖线发展中的基因组稳定性的守护者.
METTL3和YTHDF2在调节L1元素和促进生殖干细胞分化方面发挥着至关重要的作用.
与A相关的m6基因的失调可能会导致与介质性停产相关的男性不孕症.

关键词:

人类生殖线的发育过程第1行逆转录在METTL3中,METTL3是METTL3的第一个类型.m6A 修改的修改.

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