Single-cell and spatial heterogeneity landscapes of mature epicardial cells

Du, Jianlin; Deng, Haijun; Huang, Rongzhong; Liu, Bin; Xiong, Tianhua; Long, Xianglin; Zhang, Ling; Li, Yingrui; Qiang, Sheng

doi:10.1016/j.jpha.2023.07.011

Cited by 7 publications

(8 citation statements)

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“…94 Acute activation of the epicardium was first observed in the early postnatal mice after injury, as evidenced by increased expression of epicardial markers Aldh1a2 and Wt1 7 days after ventricular resection, 94 similarly observed in zebrafish injury models. Single-cell transcriptomics confirmed the presence of mesothelial-derived epicardial 97 During the regenerative phases of injured neonatal hearts, epicardial cells undergo proliferation and display distinct MI-induced gene signatures. 98 Single-cell assay for transposase-accessible chromatin sequencing revealed an enrichment of transcription factor motifs associated with MI-induced epicardial genes, including KLF14 during regeneration following injury of P1 hearts and FOSL1, BACH2, and MAFK after injury at P8.…”

Section: Neonatal Mammalian Modelsmentioning

confidence: 82%

Exploring the Function of Epicardial Cells Beyond the Surface

Wong,

Martinez,

Quijada

2024

Circulation Research

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The epicardium, previously viewed as a passive outer layer around the heart, is now recognized as an essential component in development, regeneration, and repair. In this review, we explore the cellular and molecular makeup of the epicardium, highlighting its roles in heart regeneration and repair in zebrafish and salamanders, as well as its activation in young and adult postnatal mammals. We also examine the latest technologies used to study the function of epicardial cells for therapeutic interventions. Analysis of highly regenerative animal models shows that the epicardium is essential in regulating cardiomyocyte proliferation, transient fibrosis, and neovascularization. However, despite the epicardium’s unique cellular programs to resolve cardiac damage, it remains unclear how to replicate these processes in nonregenerative mammalian organisms. During myocardial infarction, epicardial cells secrete signaling factors that modulate fibrotic, vascular, and inflammatory remodeling, which differentially enhance or inhibit cardiac repair. Recent transcriptomic studies have validated the cellular and molecular heterogeneity of the epicardium across various species and developmental stages, shedding further light on its function under pathological conditions. These studies have also provided insights into the function of regulatory epicardial-derived signaling molecules in various diseases, which could lead to new therapies and advances in reparative cardiovascular medicine. Moreover, insights gained from investigating epicardial cell function have initiated the development of novel techniques, including using human pluripotent stem cells and cardiac organoids to model reparative processes within the cardiovascular system. This growing understanding of epicardial function holds the potential for developing innovative therapeutic strategies aimed at addressing developmental heart disorders, enhancing regenerative therapies, and mitigating cardiovascular disease progression.

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Section: Neonatal Mammalian Modelsmentioning

confidence: 82%

Exploring the Function of Epicardial Cells Beyond the Surface

Wong,

Martinez,

Quijada

2024

Circulation Research

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“…Our current understanding of the underlying molecular mechanisms remains poorly explored. However, the advent of novel technological tools such as single-cell and spatial transcriptomics will certainly enhance our understanding [24,25,[89][90][91]. In this context, single-cell transcriptomics have already revealed substantial gene expression differences between human embryonic and postnatal epicardial cells [24,25] and identified novel players in epicardial EMT [89,91].…”

Section: Discussionmentioning

confidence: 99%

“…However, the advent of novel technological tools such as single-cell and spatial transcriptomics will certainly enhance our understanding [24,25,[89][90][91]. In this context, single-cell transcriptomics have already revealed substantial gene expression differences between human embryonic and postnatal epicardial cells [24,25] and identified novel players in epicardial EMT [89,91]. Additionally, the generation of novel experimental models based on organoids or spheroids, but specifically applied to the multipotential epicardium, i.e., epicardioids, as reported by Meier et al [92], will further widen our understanding of the contribution of the epicardium to cardiac diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, previous studies have shown, in mice, that the extracellular matrix (ECM) is a crucial factor in EMT and EPDC generation during cardiac development [27]. In this sense, during development, an epicardial gene marker, epidermal growth factor-containing fibulin extracellular matrix protein 1 (Efemp1), showed increased and maintained expression in the mature epicardium, thus playing an important role in the mature epicardium by regulating ECM signaling pathways [25].…”

Section: Origin and Derivatives Of The Epicardiummentioning

confidence: 99%

“…Unlike in development, the postnatal mammalian epicardium seems to be a dormant single-cell layer, probably due, at least in part, to the fact that embryonic genes involved in epicardial activation, such as WT1, Tbx18, Tcf21 and Raldh2, are severely down-regulated [23,24]. However, more recent studies [25] integrating single-cell sequencing and spatial transcriptome technology revealed that several markers, including Wt1, Tbx18, Upk1b and Upk3b, were expressed during development in both the epicardium from embryonic epicardial tissue (EET) and the postnatal epicardial tissue (PET). Nevertheless, some other genes, just like Nnat and Tcf21, presented high expression in EET but not in PET, thus revealing the cellular and temporal heterogeneity of epicardial cells during development.…”

Section: Origin and Derivatives Of The Epicardiummentioning

confidence: 99%

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Deciphering the Involvement of the Epicardium in Cardiac Diseases

Carmona,

López-Sánchez,

García-Martinez

et al. 2023

Hearts

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The epicardium is a very dynamic cardiac layer with pivotal contributions during cardiogenesis, acting in the postnatal period as an apparently dormant single-cell layer. In mammalian embryos, the epicardium, which originates form the proepicardium, translocates into the pericardial cavity and subsequently rests on the surface of the myocardium. Later, it gives rise to the epicardium-derived cells, which migrate into subepicardial space, invade the developing myocardium, promoting its growth, and contribute to different cell types. Anomalies in the process of epicardial development, the generation of epicardium-derived cells and their signaling mechanisms in different experimental models lead to defective cardiac development, reminiscent of human congenital heart diseases. Furthermore, recent studies have reported that epicardial derivates in adults, i.e., epicardial adipose tissue, are associated with electrophysiological cardiovascular anomalies. Herein, we provide a state-of-the-art review focusing on both congenital and adult heart diseases associated with epicardial development.

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