Unveiling Human Cardiac Fibroblast Membrane Proteome

Abstract

Cardiac fibroblasts (CFs) are one of the main cell populations in the heart and play important roles in tissue homeostasis and myocardial fibrosis. The study of these cells has been hampered by the lack of reliable membrane markers: none of the antigens currently used for characterization and isolation of CFs is unique for this cell type. This issue has also raised doubts regarding a distinct identity of cardiac fibroblasts when compared to other myocardium cell populations with similar morphologies. In this work, we report a comprehensive description and functional analysis of human CFs (hCFs) membraneenriched fraction proteome by advanced mass spectrometry-based proteomic tools. A total number of 1478 proteins were identified, including 774 membrane proteins (52%). We also report the identification of a subset of 30 membrane proteins that in this workflow were only identified in hCFs by comparison with the membrane-enriched proteome lists of human cardiac stem cells, human mesenchymal stem cells, and human dermal fibroblasts. The data reported in this work are a valuable source of information for further studies aiming at defining a membrane molecular signature of human cardiac fibroblasts (hCFs), and a step forward in research regarding membrane proteins with key roles in hCF function in homeostasis and disease.

Role of PDGF-A/B Ligands in Cardiac Repair After Myocardial Infarction

“…PDGFRα is expressed by widely distributed non-vascular interstitial fibroblasts ( Ivey and Tallquist, 2016 ; Sebastiao et al, 2018 ) including a subpopulation of cells marking enriched MSC populations in all organs/tissues ( Farahani and Xaymardan, 2015 ; Ivey and Tallquist, 2016 ). Detailed single-cell RNA (scRNA) analysis has shown that while the PDGFRα cells in the mouse hearts are mostly fibroblastic in nature, a small population co-expresses endothelial marker CD31, and a further minor population co-expresses macrophage markers.…”

Human cardiac progenitor cell activation and regeneration mechanisms: exploring a novel myocardial ischemia/reperfusion in vitro model

“…The hCPCs employed in this work are not the same population involved in this controversy and were isolated and cultured using a different protocol (Patent WO2014141220A1), which was also used for the isolation of the hCPC population recently evaluated for the allogeneic treatment of AMI in CAREMI clinical trial (NCT02439398). Importantly, these cells were already extensively characterized at the immunomodulatory [14–17], total proteome [18], membrane proteome [19, 20], and secretome [21] levels. The regenerative benefit of these cells was studied in vivo in pig AMI animal model [22, 23].…”

Fibroblast-Specific Proteotranscriptomes Reveal Distinct Fibrotic Signatures of Human Sinoatrial Node in Nonfailing and Failing Hearts

“…miRNA-1306-5p is known to be released by the myocardium, and its circulating levels are considered a biomarker of HF. 43 We found that miRNA-1306-5p is expressed in human SAN fibroblasts as well, with higher levels in untreated non-HF SAN fibroblasts. Network analyses also showed that many of the significantly different SAN miRNAs paired inversely with selected ECM and profibrotic genes, which predicted potential miRNA-mediated regulation of these genes and SAN fibrosis (Figure 7).…”