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Genetic lineage tracing defines myofibroblast origin and function in the injured heart
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Genetic lineage tracing defines myofibroblast origin and function in the injured heart
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Journal Article
Genetic lineage tracing defines myofibroblast origin and function in the injured heart
2016
Overview
Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction (MI) and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell type in terms of their origins and functional effects
in vivo
. Here we generate
Postn
(periostin) gene-targeted mice containing a tamoxifen-inducible Cre for cellular lineage-tracing analysis. This
Postn
allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Lineage tracing with four additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin
+
myofibroblasts reduces collagen production and scar formation after MI. Periostin-traced myofibroblasts also revert back to a less-activated state upon injury resolution. Our results define the myofibroblast as a periostin-expressing cell type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21
+
tissue-resident fibroblasts.
The origin and fate of myofibroblasts, the cells responsible for cardiac remodelling and fibrosis, is controversial. Here the authors show that cardiac myofibroblasts express periostin, derive exclusively from tissue-resident fibroblasts, are necessary for scar formation after injury, and can revert back to a less-activated state upon injury resolution.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/35
/ 64
/ 64/60
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - metabolism
/ Cell Adhesion Molecules - genetics
/ Cell Adhesion Molecules - metabolism
/ Collagen
/ Female
/ Fibrosis
/ Healing
/ Heart
/ Humanities and Social Sciences
/ Injuries
/ Male
/ Mice
/ Muscles
/ Myocardial Infarction - pathology
/ Science
