胎盘生长因子在心脏发育过程中对心肌生成和血管生成起着双重作用
Nevin Witman1, Chikai Zhou1, Timm Häneke1
1Department of Cell and Molecular Biology, Karolinska Institutet, A6 Biomedicum, SE-171 77, Stockholm, Sweden.
Nature communications
|September 5, 2023
概括
胎盘生长因子 (PLGF) 通过增强心肌细胞和内皮细胞的产生促进心脏发育. 这项研究揭示了PLGF.
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
- 干细胞生物学 干细胞生物学
背景情况:
- 心脏生长因子对心脏发育至关重要.
- 胎盘生长因子 (PLGF) 已知具有血管性作用,但其在心脏生成中的作用尚不清楚.
研究的目的:
- 研究PLGF在人类心脏发育和心脏生成中的作用.
- 探索PLGF对心肌细胞 (CM) 和内皮细胞 (EC) 与人类胚胎干细胞 (hESC) 的分化的影响.
主要方法:
- 来自人类和灵长类动物胚胎心脏的单细胞RNA测序数据的分析.
- 在hESC分化过程中应用编码PLGF的化学修饰mRNAs (modRNAs).
- 在实验室中对PLGF进行遗传删除.
- 在活体中评估PLGF modRNA对小鼠模型中的心肌移植的影响.
主要成果:
- 在胚胎心脏中,PLGF表现出双相表达模式,这种表达模式在早期的祖细胞和后来的血管细胞中发现.
- 在早期的PLGF modRNA应用显著增加了CM和EC生产.
- 在实验室中,PLGF的遗传除损害了CMs,光滑肌细胞 (SMCs) 和ECs的生成.
- 在体内研究证实了PLGF modRNA对心肌移植发育的有益影响.
结论:
- 在心脏发育过程中,PLGF表现出双重心肌原生和血管原生效应.
- PLGF是心肌细胞和血管细胞分化的关键调节者.
- PLGF modRNA代表了心脏再生的潜在治疗策略.
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