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Jiajun Sun^1,2,3, Yanqiu Wang^1,2,3, Hui Fu^1,2,3

¹Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

|November 14, 2023

概括

甲基转移酶样RNA3 (Mettl3) 对于胰腺发育至关重要. 缺少它会通过影响基因素脱乙酶1 (Hdac1) 和Wnt/Notch信号来破坏内分泌细胞的形成,从而提供潜在的糖尿病治疗策略.

科学领域:

发展生物学发展生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
内分泌学在内分泌学.

背景情况:

已知m6ARNA修饰在β细胞功能中的作用,但其对胰腺发育和内分泌分化的影响尚不清楚.
类似RNA甲基转移酶3 (Mettl3) 是m6ARNA修饰中的一个关键酶.

研究的目的:

研究Mettl3在胰腺发育和内分泌分化的作用.
阐明Mettl3调节这些过程的分子机制.

主要方法:

生成的转基因小鼠与Mettl3在Pdx1+胰腺原生细胞中被特异删除.
分析了不同发育阶段的胰腺组织学,小岛质量和细胞群 (Ngn3+,Sox9+).
用于体外胚胎胰腺培养来研究信号通路.

主要成果:

在胰腺原始体中缺乏Mettl3的小鼠患上高血糖症,低胰岛素症,胰腺缩,岛屿质量减少和导管形成增加.
Mettl3的删除导致了Ngn3+内分泌前体的丧失和Sox9+管道前体的增加.
基因组脱乙酶1 (Hdac1) 被确定为直接的m6A标;其失调激活了Wnt/Notch信号,阻断了内分泌分化.

结论:

在发育过程中,Mettl3对于胰腺内分泌系的确定至关重要.
梅特尔3-Hdac1-Wnt/Notch信号轴对于调节双强原生转变和内分泌分化至关重要.
针对这一轴可能为糖尿病治疗提供新的治疗策略.

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