Origin, development, and differentiation of cardiac fibroblasts

Abstract

Cardiac fibroblasts are the most abundant cell in the mammalian heart. While they have been historically underappreciated in terms of their functional contributions to cardiac development and physiology, they and their activated form, myofibroblasts, are now known to play key roles in both development and disease through structural, paracrine, and electrical interactions with cardiomyocytes. The lack of specific markers for fibroblasts currently convolutes the study of this dynamic cell lineage, but advances in marker analysis and lineage mapping technologies are continuously being made. Understanding how to best utilize these tools, both individually and in combination, will help to elucidate the functional significance of fibroblast-cardiomyocyte interactions in vivo. Here we review what is currently known about the diverse roles played by cardiac fibroblasts and myofibroblasts throughout development and periods of injury with the intent of emphasizing the duality of their nature. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium ".

Keywords: Cardiac fibroblast; Development; Embryo; Fibrosis; Marker analysis; Myofibroblast.

Figure 1. MyoCFs originate from a variety of sources and exhibit both adaptive as well as detrimental effects upon the healing process

MyoCFs can be derived from the endothelium and epithelium via mesenchymal transition (EMT and EndMT), as well as from perivascular cells, circulating monocytes and bone marrow-derived progenitors, particularly in the context of injury. Resident CFs also contribute to this pool by undergoing a low level of turnover. The resultant myoCFs are then involved in both constructive (black text) as well as harmful (red text) effects on the myocardium of the injured heart.