多系谱转录因子ISL1通过与NKX2.5的相互作用控制心肌细胞命运
Bonnie E J Maven1, Casey A Gifford2, Melanie Weilert3
1Gladstone Institutes, San Francisco, CA, USA; Developmental and Stem Cell Biology PhD Program, University of California, San Francisco, San Francisco, CA, USA; Roddenberry Center for Stem Cell Biology at Gladstone, San Francisco, CA, USA.
Stem cell reports
|October 20, 2023
概括
ISLET1 (ISL1) 转录因子与NKX2.5和GATA4合作,控制心脏发育. 这种组合代码决定了ISL1.
科学领域:
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
- 干细胞生物学 干细胞生物学
背景情况:
- 先天性心脏病与转录因子 (TF) 干扰有关.
- ISLET1 (ISL1) 是一个对心脏,神经元和胰腺发育至关重要的TF.
- 通过与其他TF的相互作用来调解ISL1的血统特异性作用,但心脏伴侣仍然未被识别.
研究的目的:
- 为了确定ISL1在心脏原始体 (CPs) 中的相互作用伙伴.
- 了解ISL1如何通过组合相互作用实现谱系特异性.
主要方法:
- 在人类诱导的多能干细胞衍生CP和运动神经元原始体 (MNP) 中测试的ISL1基因组占用率.
- 使用深度学习方法BPNet预测与ISL1绑定相关的TF动机.
- 经过实验验证的TF共占和TF去除/过度表达的影响.
主要成果:
- NKX2.5和GATA动机与CP的ISL1占用率最强烈相关.
- 近三分之二的ISL1-bound站点被NKX2.5和/或GATA4.4共同占领.
- 删除NKX2.5改变了CP中的ISL1结合;MNP中的NKX2.5过度表达将ISL1招募到CP特定的位置.
结论:
- ISL1通过涉及NKX2.5和GATA因子的组合代码指导血统选择.
- 这个代码决定了ISL1的基因组占用率和转录活动.
- 这些发现提供了对先天性心脏病病因和心脏发育调节的洞察.
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