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将Shox2的形态遗传调节功能的分离与其在节发育中的细胞命运守护者作用
Hua Li1,2,3, Qinghuang Tang4,5, Tianfang Yang4
1Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University, Fujian Medical University, Fuzhou, Fujian Province, 350122, PR China. hli28@tulane.edu.
Communications biology
|March 30, 2024
概括
Shox2对于鼻腔节点 (SAN) 的发育和功能至关重要. 它的失活拯救了心脏起器细胞的命运,但不是SAN结构,揭示了细胞决定与形态发生的不同作用.
科学领域:
- 心血管生物学 心血管生物学
- 发展生物学 发展生物学
- 分子心脏病学分子心脏病学
背景情况:
- 鼻腔节点 (SAN) 是心脏的主要起器,对心律至关重要.
- 众所周知,Shox2对SAN形态发生和功能至关重要,突变导致hypoplasticSAN和失败的起器细胞分化.
- Shox2 和 Nkx2-5 相互对抗,以调节 SAN 心脏起器细胞命运.
研究的目的:
- 调查Shox2在SAN细胞命运决定和形态发生中的独特作用.
- 在SAN开发中阐明Shox2和Nkx2-5之间的功能关系.
- 了解Shox2在发展中SAN中的调节功能背后的分子机制.
主要方法:
- 在SAN中生成Shox2和Nkx2-5双淘汰 (dKO) 鼠标模型.
- 在突变和野生型胚胎中分析SAN结构和心脏起器细胞分化.
- 单细胞RNA测序 (scRNA-seq) 用于在发育中的SAN细胞中描述基因表达和细胞状态.
主要成果:
- 在Shox2突变体 (dKO) 中同时禁用Nkx2-5挽救了心脏起器细胞命运,但没有纠正SAN低成形,将细胞命运与形态发生脱.
- scRNA-seq显示Shox2缺陷的SAN原始细胞未能激活节拍程序,仍然处于原始状态.
- 野生类型和dKO SAN细胞都表现出正常的节拍细胞命运和类似的细胞状态,突出显示Shox2在保护这一过程中的作用.
结论:
- 通过Shox2-Nkx2-5对抗机制,Shox2充当了通过Shox2-Nkx2-5对抗机制来决定细胞命运的保护因素,而不是决定因素.
- 在确保节拍细胞命运中的Shox2的功能与其在调节SAN形态发生中的作用分开.
- 这些发现为管理心脏起器发育的复杂监管网络提供了关键的见解.
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