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综合建模框架揭示了转录因子,miRNA和lncRNA在心脏发育动态上的共同调节

Shumin Li¹, Bin Yan^1,2, Binbin Wu^3,4

¹Department of Computer Science, The University of Hong Kong, Pokfulam, Hong Kong, China.

Stem cell research & therapy

|September 13, 2023

概括

这项研究引入了一个新的框架,心脏基因调节建模 (CGRM),以了解转录因子,微RNA和长非编码RNA如何调节心脏发育. 早期阶段的细胞表现出保存的网络,而晚期的细胞在体外和体内发育之间存在显著分歧.

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
基因组学就是基因组学.

背景情况:

了解心脏发育需要剖析转录因子 (TF),微RNA (miRNA) 和长非编码RNA (lncRNA) 之间的复杂相互作用.
目前的计算方法不足以捕捉心脏基因表达的动态控制由各种调节因素,包括非编码RNA.

研究的目的:

开发一个集成的计算框架,心脏基因调节建模 (CGRM),以推断复杂的TF-ncRNA基因调节网络.
为了比较这些网络的早期和晚期心肌细胞 (CMs) 来自体外人类多能干细胞 (hPSCs) 和体内人类心脏发育.

主要方法:

将综合逻辑TRN和监管组件分析生物信息平台纳入CGRM框架.
应用CGRM分析TF-ncRNA网络在hPSC衍生的CM和体内心脏CM不同发育阶段.

主要成果:

在早期的CMs (hPSC衍生和体内) 中发现了保存的TF-ncRNA网络,主要由MESP1,miR-1,miR-23,NEAT1和MALAT1调节.
晚期的CM显示了监管网络的显著分歧,其中GATA6,HAND2,miR-200c,NEAT1和MALAT1具有关键性.
与亡,细胞循环,增殖和跨膜传输相关的基因在体外和体外晚期CMs之间有显著差异.

结论:

人类多能干细胞衍生心肌细胞 (hPSC-CMs) 在早期发育中表现出细胞自主调节,这与体内发育随着时间的推移不同.
CGRM有效地揭示了基于细胞导向和环境依赖的CM开发的动态调节相互作用.
这种方法为分析心脏病机制和细胞调节系统在其他生物医学领域提供了基础.

关键词:

心脏的发育和功能.数据整合数据集成基因监管网络基因监管网络转录因子转录因子在 lncRNAs 中.这就是miRNAs.

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