Environmental Cues Facilitate Maturation and Patterning of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

IF 2.5 Q3 CELL BIOLOGY Cellular Physiology and Biochemistry Pub Date : 2024-10-04 DOI:10.33594/000000730
Enrique Coca, Scott Cho, Christopher Kauffman, Alonzo D Cook, Martin Tristani-Firouzi, Natalia S Torres
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Abstract

Background/aims: Advances in induced pluripotent stem cell (iPSC) technology allow for reprogramming of adult somatic cells into stem cells from which patient- and disease-specific cardiomyocytes (CMs) can be derived. Yet, the potential of iPSC technology to revolutionize cardiovascular research is limited, in part, by the embryonic nature of these cells. Here, we test the hypothesis that decellularized porcine left ventricular extracellular cardiac matrix (ECM) provides environmental cues that promote transcriptional maturation and patterning of iPSC-CMs in culture.

Methods: Cardiac progenitor cells were plated on ECM or standard tissue plates (2D monolayer) for 30 days, after which CM orientation and single cell transcriptomics were evaluated using confocal imaging and singe cell RNA-sequencing, respectively.

Results: Cardiac progenitors differentiated on left ventricular ECM formed longitudinal fibers that differed quantitatively from progenitors differentiated in standard 2D conditions. Unsupervised clustering of single cell transcriptomics identified a CM cluster expressing a higher level of genes related to CM maturation. CMs differentiated on ECM were overrepresented in this cluster, indicating a bias toward CM maturation, compared to cells differentiated in standard 2D monolayer conditions.

Conclusion: Our data suggest that environmental cues related to the left ventricular ECM may promote differentiation to a more mature CM state compared to cells differentiated on a standard 2D monolayer, while facilitating organization into longitudinal micro-fibers. Our study highlights the utility of ECM as a differentiation substrate to promote CM maturation and fiber orientation in vitro .

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环境线索促进人类诱导多能干细胞衍生心肌细胞的成熟和分型
背景/目的:诱导多能干细胞(iPSC)技术的进步可将成人体细胞重编程为干细胞,并从中衍生出患者和疾病特异性心肌细胞(CM)。然而,iPSC 技术彻底改变心血管研究的潜力部分受限于这些细胞的胚胎性质。在这里,我们验证了这样一个假设:脱细胞猪左心室细胞外基质(ECM)提供环境线索,促进 iPSC-CMs 在培养过程中的转录成熟和模式化:方法:将心脏祖细胞在 ECM 或标准组织板(二维单层)上培养 30 天,然后分别使用共焦成像和单细胞 RNA 序列对 CM 定向和单细胞转录组学进行评估:结果:在左心室 ECM 上分化的心脏祖细胞形成的纵向纤维在数量上与在标准二维条件下分化的祖细胞不同。单细胞转录组学的无监督聚类确定了一个表达与CM成熟相关的高水平基因的CM集群。与在标准二维单层条件下分化的细胞相比,在ECM上分化的CM在该集群中的比例过高,这表明CM偏向于成熟:我们的数据表明,与在标准二维单层上分化的细胞相比,与左心室 ECM 相关的环境线索可促进 CM 向更成熟的状态分化,同时有利于组织成纵向微纤维。我们的研究强调了 ECM 作为分化基质在体外促进 CM 成熟和纤维定向的效用。
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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
86
审稿时长
1 months
期刊介绍: Cellular Physiology and Biochemistry is a multidisciplinary scientific forum dedicated to advancing the frontiers of basic cellular research. It addresses scientists from both the physiological and biochemical disciplines as well as related fields such as genetics, molecular biology, pathophysiology, pathobiochemistry and cellular toxicology & pharmacology. Original papers and reviews on the mechanisms of intracellular transmission, cellular metabolism, cell growth, differentiation and death, ion channels and carriers, and the maintenance, regulation and disturbances of cell volume are presented. Appearing monthly under peer review, Cellular Physiology and Biochemistry takes an active role in the concerted international effort to unravel the mechanisms of cellular function.
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