Cardiac fibroblasts: more than mechanical support

Abstract

Fibroblasts are cells with a structural function, synthesizing components of the extracellular matrix. They are accordingly associated with various forms of connective tissue. During cardiac development fibroblasts originate from different sources. Most derive from the epicardium, some derive from the endocardium, and a small population derives from the neural crest. Cardiac fibroblasts have important functions during development, homeostasis, and disease. However, since fibroblasts are a very heterogeneous cell population no truly specific markers exist. Therefore, studying them in detail is difficult. Nevertheless, several lineage tracing models have been widely used. In this review, we describe the developmental origins of cardiac fibroblasts, comment on fibroblast markers and related lineage tracing approaches, and discuss the cardiac cell composition, which has recently been revised, especially in terms of non-myocyte cells.

Single-Cell Transcriptome Analysis Maps the Developmental Track of the Human Heart

“…The expression of ECM genes increased during CM and cardiac fibroblast maturation ( Figures 2C-2F and 3), sharply increasing from 5W to 6W. ECM proteins were previously considered to be derived primarily from fibroblasts and to provide only physical support for the cells; however, a growing body of evidence indicates that ECM proteins may be generated from CMs or other cell types as well, and these proteins have a wide variety of effects on cellular processes, including cell proliferation, differentiation, and migration, especially during embryogenesis (Doppler et al, 2017;Lockhart et al, 2011). Therefore, the synergistic increase in a large number of ECM proteins may contribute to CM differentiation and maturation.…”

“…Expression levels of mitosis-related genes, such as AURKB, CDK1, and UBE2C, were also decreased ( Figure S4F). The ECM plays a vital role in embryonic heart development because it provides structural support for cardiac cells, cellcell signaling, and cell migration and contributes to the regulation of cell proliferation and differentiation (Doppler et al, 2017). In fibroblasts, relative expression levels of ECM genes also gradually increased with heart development (Figures 4E and 4F).…”

Generation of Heart Organoids Modeling Early Human Cardiac Development Under Defined Conditions

“…Most cardiac fibroblasts in embryonic development arise from the PEO 57,65,66 , highlighting the necessity of proepicardial induction in developmental heart models. Immunofluorescence analysis of our hHOs revealed the presence of cardiac fibroblast markers including the membrane glycoprotein Thy1, which is involved in cell-cell and cell-matrix adhesion 66,67 , and the intermediate filament protein Vimentin, typically seen in cells of mesenchymal lineage 67 . Other cardiac fibroblast markers were found in the hHOs via RNA-sequencing analysis, including DDR2 66 which plays an important role in EMT and the FHF marker PDGFRα which is crucial for vascularization during development and is also a strong marker of cardiac fibroblasts 67 .…”

Cardiac Stem Cell Therapy, Resident Progenitor Cells and the role of Cellular Signalling; a Review

“…Because cardiac fibroblasts represent a heterogenous population with no specific cell markers, they are among the least characterised cell types relevant to heart health [37]. Although adult CFs promote cardiomyocyte hypertrophy, it has been shown that embryonic CFs contribute to proliferation of CMs through paracrine signalling [38].…”