View from the heart: cardiac fibroblasts in development, scarring and regeneration

Furtado, Milena B.; Nim, Hieu T.; Boyd, Sarah; Rosenthal, Nadia

doi:10.1242/dev.120576

Cited by 125 publications

(110 citation statements)

References 124 publications

(164 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2F) . This is consistent with previously reported data demonstrating that GATA4 is crucial for heart formation during embryonic development and strongly implicated in congenital heart diseases (Butler et al, 2010; Furtado et al, 2016; Garg et al, 2003), and suggests a cardiac endothelium identity for the CMEC-derived endothelial cells.…”

Section: Resultssupporting

confidence: 93%

Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells

et al. 2017

View full text Add to dashboard Cite

Cardiomyocytes and endothelial cells in the heart are in close proximity and in constant dialogue. Endothelium regulates the size of the heart, supplies oxygen to the myocardium and secretes factors that support cardiomyocyte function. Robust and predictive cardiac disease models that faithfully recapitulate native human physiology in vitro would therefore ideally incorporate this cardiomyocyte-endothelium crosstalk. Here, we have generated and characterized human cardiac microtissues in vitro that integrate both cell types in complex 3D structures. We established conditions for simultaneous differentiation of cardiomyocytes and endothelial cells from human pluripotent stem cells following initial cardiac mesoderm induction. The endothelial cells expressed cardiac markers that were also present in primary cardiac microvasculature, suggesting cardiac endothelium identity. These cell populations were further enriched based on surface markers expression, then recombined allowing development of beating 3D structures termed cardiac microtissues. This in vitro model was robustly reproducible in both embryonic and induced pluripotent stem cells. It thus represents an advanced human stem cell-based platform for cardiovascular disease modelling and testing of relevant drugs.

show abstract

Section: Resultssupporting

confidence: 93%

Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Whether the proliferative capacity of cCFU-F cells in vitro reflects their selfrenewal and progenitor status in vivo requires investigation, and it remains to be demonstrated whether any PDGFRα + cells in the adult mammalian heart have cardiomyogenic potential that could be augmented in a therapeutic setting. Furthermore, the notion of a 'living scar' and the many roles of cardiac stromal cells and descendant myofibroblasts is well established and targeting different aspects of fibrogenesis is an active area of research (Furtado et al, 2016).…”

Section: Cre−ert2mentioning

confidence: 99%

“…The origin of stromal fibroblasts and myofibroblasts is an important consideration in this Review, because in addition to providing a cardiac scaffold and structural integrity to the heart, stromal cells and myofibroblasts regulate organ development, wound healing, stem cell niches and inflammation (Furtado et al, 2016). An early CRE-based lineage-tracing experiment suggested that a subset of cardiac stromal fibroblasts arise de novo via endothelial-tomesenchymal transition (EndMT) from adult endothelial cells (Zeisberg et al, 2007).…”

Section: Origins and Plasticity Of Cardiac Fibroblastsmentioning

confidence: 99%

Developmental origin and lineage plasticity of endogenous cardiac stem cells

et al. 2016

View full text Add to dashboard Cite

Over the past two decades, several populations of cardiac stem cells have been described in the adult mammalian heart. For the most part, however, their lineage origins and in vivo functions remain largely unexplored. This Review summarizes what is known about different populations of embryonic and adult cardiac stem cells, including KIT + , PDGFRα + , ISL1 + and SCA1 + cells, side population cells, cardiospheres and epicardial cells. We discuss their developmental origins and defining characteristics, and consider their possible contribution to heart organogenesis and regeneration. We also summarize the origin and plasticity of cardiac fibroblasts and circulating endothelial progenitor cells, and consider what role these cells have in contributing to cardiac repair.

show abstract

“…CFs significantly contribute to multiple aspects of cardiac function and disease [53], particularly via modulation of fibrotic remodeling in the heart following injury [10], [54] and [55]. To examine the consequences of GRK2 loss in CFs for cardiac function, authors used tamoxifen-inducible collagen1α2-CreER(T)/GRK2 fl/fl mice (GRK2 fKO mice).…”

Section: Gβγ-grk2 Signaling Manipulation As a Strategy To Treat Camentioning

confidence: 99%

Targeting GPCR-Gβγ-GRK2 signaling as a novel strategy for treating cardiorenal pathologies

Rudomanova

Blaxall

2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

The pathologic crosstalk between the heart and kidney is known as cardiorenal syndrome (CRS). While the specific mechanisms underlying this crosstalk remain poorly understood, CRS is associated with exacerbated dysfunction of either or both organs and reduced survival. Maladaptive fibrotic remodeling is a key component of both heart and kidney failure pathogenesis and progression. G-protein coupled receptor (GPCR) signaling is a crucial regulator of cardiovascular and renal function. Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gβγ subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation. Targeting this pathologic Gβγ-GRK2 interaction has been suggested as a possible strategy for the treatment of HF. In the current review, we discuss recent updates in understanding the role of GPCR-Gβγ-GRK2 signaling as a crucial mediator of maladaptive organ remodeling detected in HF and kidney dysfunction, with specific attention to small molecule-mediated inhibition of pathologic Gβγ-GRK2 interactions. Further, we explore the potential of GPCR-Gβγ-GRK2 signaling as a possible therapeutic target for cardiorenal pathologies.

show abstract

View from the heart: cardiac fibroblasts in development, scarring and regeneration

Cited by 125 publications

References 124 publications

Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells

Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells

Developmental origin and lineage plasticity of endogenous cardiac stem cells

Targeting GPCR-Gβγ-GRK2 signaling as a novel strategy for treating cardiorenal pathologies

Contact Info

Product

Resources

About