人心源性祖细胞与心外膜细胞的直接共培养诱导心肌细胞增殖并减少肌节组织。
Direct coculture of human pluripotent stem cell-derived cardiac progenitor cells with epicardial cells induces cardiomyocyte proliferation and reduces sarcomere organization.
机构信息
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, United States.
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, United States.
出版信息
J Mol Cell Cardiol. 2022 Jan;162:144-157. doi: 10.1016/j.yjmcc.2021.09.009. Epub 2021 Sep 22.
Epicardial cells (EpiCs) are necessary for myocardium formation, yet little is known about crosstalk between EpiCs and cardiomyocytes (CMs) during development and the potential impact of EpiCs on CM maturation. To investigate the effects of EpiCs on CM commitment and maturation, we differentiated human pluripotent stem cells (hPSCs) to cardiac progenitor cells (CPCs) and EpiCs, and cocultured EpiCs and CPCs for two weeks. When EpiCs were allowed to form epicardial-derived cells, we observed increased expression of cTnI in developing CMs. In the presence of the TGFβ inhibitor A83-01, EpiCs remained in the epicardial state and induced CM proliferation, increased MLC2v expression, and led to less organized sarcomeres. These effects were not observed if CPCs were treated with EpiC-conditioned medium or if CPCs were indirectly cocultured with EpiCs. Finally, single cell RNA sequencing identified that EpiC-CPC coculture had bi-directional effects on transcriptional programs in EpiCs and CMs, and biased EpiC lineages from a SFRP2-enriched population to a DLK1- or C3-enriched population. This work suggests important crosstalk between EpiCs and CMs during differentiation which can be used to influence cell fate and improve the ability to generate cardiac cells and tissues for in vitro models and development of cardiac cellular therapies.
心外膜细胞(EpiCs)对于心肌形成是必需的,但在发育过程中,EpiCs 与心肌细胞(CMs)之间的相互作用以及 EpiCs 对 CM 成熟的潜在影响知之甚少。为了研究 EpiCs 对 CM 分化和成熟的影响,我们将人多能干细胞(hPSCs)分化为心脏祖细胞(CPCs)和 EpiCs,并将 EpiCs 和 CPCs 共培养两周。当 EpiCs 形成心外膜衍生细胞时,我们观察到发育中的 CM 中 cTnI 的表达增加。当存在 TGFβ抑制剂 A83-01 时,EpiCs 仍保持在心外膜状态,并诱导 CM 增殖,增加 MLC2v 的表达,导致肌节排列更不规则。如果 CPCs 用 EpiC 条件培养基处理或 CPCs 与 EpiC 间接共培养,则不会观察到这些影响。最后,单细胞 RNA 测序鉴定出 EpiC-CPC 共培养对 EpiCs 和 CMs 中的转录程序具有双向影响,并使来自 SFRP2 富集群体的 EpiC 谱系偏向于 DLK1 或 C3 富集群体。这项工作表明,在分化过程中 EpiCs 和 CMs 之间存在重要的相互作用,可用于影响细胞命运,并提高体外模型中生成心脏细胞和组织以及心脏细胞治疗的能力。
相似文献
J Mol Cell Cardiol. 2024-2
Biochim Biophys Acta Mol Cell Res. 2019-8-28
引用本文的文献
Front Bioeng Biotechnol. 2024-8-15
Adv Sci (Weinh). 2023-9
本文引用的文献
Front Cardiovasc Med. 2020-10-15
Bioengineering (Basel). 2020-8-10