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抑制Wnt活动改善了体细胞核转移胚胎的周植入发育

Yanhe Li¹, Caihong Zheng², Yingdong Liu¹

¹Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

National science review

|August 18, 2023

概括

持久的Wnt信号阻碍体细胞核转移 (SCNT) 胚胎发育,因为它阻断了多能转换. 抑制Wnt信号提高了克隆效率和发展潜力,克服了SCNT的一个关键障碍.

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.
生殖生物学生殖生物学

背景情况:

体细胞核转移 (SCNT) 可以将分化细胞重新编程为全能.
SCNT胚胎发育改善了植入前期,但植入前期停产仍然存在.
在SCNT胚胎周植入失败背后的机制仍然不清楚.

研究的目的:

调查SCNT胚胎在植入前阶段停止的机制.
确定阻碍表皮质细胞发育和SCNT胚胎植入的因素.
开发提高SCNT胚胎发育潜力和克隆效率的策略.

主要方法:

开发一个用于SCNT周植入胚胎的3D体外培养系统.
对Wnt信号通路和H3K27me3在SCNT表皮质细胞中的占用率的分析.
单细胞RNA测序 (scRNA-seq) 用于评估血统发展轨迹.
操纵Wnt信号来观察对多能性和克隆效率的影响.

主要成果:

持久的Wnt信号阻断了SCNT表细胞中从原始到原始的多能性过渡.
异常的H3K27me3占用与Wnt诱导的多能性缺陷有关.
Wnt信号操纵显著改善了表皮质多能性和H3K27me3沉积.
抑制Wnt可使SCNT克隆效率提高多达9倍.
scRNA-seq证实了Wnt抑制的SCNT胚芽细胞中增强的血统发育轨迹.

结论:

持久的Wnt信号是SCNT胚胎中围植发育的关键障碍.
异常的表观遗传修饰 (H3K27me3) 导致SCNT发育缺陷.
调节Wnt信号可以克服SCNT胚胎中的多能性和表观遗传缺陷.
针对Wnt途径提供了一个有希望的策略,以提高SCNT的成功率.

关键词:

这是SCNT.他们不想做.经皮质细胞是什么?表观遗传障碍是表观遗传障碍的一种.植入植入植入植入植入植入植入植入植入纯粹的多能性就是一种多能性.预备中的多能性.重编程是重新编程.一个单细胞RNA-seqq.

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