Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice
Summary: Cardiac ischemia leads to the loss of myocardial tissue and the activation of a repair process that culminates in the formation of a scar whose structural characteristics dictate propensity to favorable healing or detrimental cardiac wall rupture. To elucidate the cellular processes underly...
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doaj-4c04a1b1b8cc4f488dda97c0c6b71aa62020-11-25T02:17:12ZengElsevierCell Reports2211-12472020-03-0130931493163.e6Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse MiceElvira Forte0Daniel A. Skelly1Mandy Chen2Sandra Daigle3Kaesi A. Morelli4Olivia Hon5Vivek M. Philip6Mauro W. Costa7Nadia A. Rosenthal8Milena B. Furtado9The Jackson Laboratory, Bar Harbor, ME 04609, USA; Corresponding authorThe Jackson Laboratory, Bar Harbor, ME 04609, USAThe Jackson Laboratory, Bar Harbor, ME 04609, USAThe Jackson Laboratory, Bar Harbor, ME 04609, USAThe Jackson Laboratory, Bar Harbor, ME 04609, USAThe Jackson Laboratory, Bar Harbor, ME 04609, USAThe Jackson Laboratory, Bar Harbor, ME 04609, USAThe Jackson Laboratory, Bar Harbor, ME 04609, USAThe Jackson Laboratory, Bar Harbor, ME 04609, USA; National Heart and Lung Institute, Imperial College London, London SW72BX, UKThe Jackson Laboratory, Bar Harbor, ME 04609, USA; Corresponding authorSummary: Cardiac ischemia leads to the loss of myocardial tissue and the activation of a repair process that culminates in the formation of a scar whose structural characteristics dictate propensity to favorable healing or detrimental cardiac wall rupture. To elucidate the cellular processes underlying scar formation, here we perform unbiased single-cell mRNA sequencing of interstitial cells isolated from infarcted mouse hearts carrying a genetic tracer that labels epicardial-derived cells. Sixteen interstitial cell clusters are revealed, five of which were of epicardial origin. Focusing on stromal cells, we define 11 sub-clusters, including diverse cell states of epicardial- and endocardial-derived fibroblasts. Comparing transcript profiles from post-infarction hearts in C57BL/6J and 129S1/SvImJ inbred mice, which displays a marked divergence in the frequency of cardiac rupture, uncovers an early increase in activated myofibroblasts, enhanced collagen deposition, and persistent acute phase response in 129S1/SvImJ mouse hearts, defining a crucial time window of pathological remodeling that predicts disease outcome. : Using single-cell transcriptional profiling of mouse hearts carrying a reporter for epicardial-derived cells, Forte et al. provide a dynamic view of cardiac interstitial responses across acute and chronic phases of remodeling post-infarction. Comparing responses on diverse genetic backgrounds reveals novel cellular and transcriptional features of cardiac rupture propensity. Keywords: myocardial infarction, single-cell biology, cardiac rupture, fibrosis, genetic diversity, heart, mouse, epicardial-derived, scRNAseq, Seurathttp://www.sciencedirect.com/science/article/pii/S2211124720301625 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elvira Forte Daniel A. Skelly Mandy Chen Sandra Daigle Kaesi A. Morelli Olivia Hon Vivek M. Philip Mauro W. Costa Nadia A. Rosenthal Milena B. Furtado |
spellingShingle |
Elvira Forte Daniel A. Skelly Mandy Chen Sandra Daigle Kaesi A. Morelli Olivia Hon Vivek M. Philip Mauro W. Costa Nadia A. Rosenthal Milena B. Furtado Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice Cell Reports |
author_facet |
Elvira Forte Daniel A. Skelly Mandy Chen Sandra Daigle Kaesi A. Morelli Olivia Hon Vivek M. Philip Mauro W. Costa Nadia A. Rosenthal Milena B. Furtado |
author_sort |
Elvira Forte |
title |
Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice |
title_short |
Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice |
title_full |
Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice |
title_fullStr |
Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice |
title_full_unstemmed |
Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice |
title_sort |
dynamic interstitial cell response during myocardial infarction predicts resilience to rupture in genetically diverse mice |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2020-03-01 |
description |
Summary: Cardiac ischemia leads to the loss of myocardial tissue and the activation of a repair process that culminates in the formation of a scar whose structural characteristics dictate propensity to favorable healing or detrimental cardiac wall rupture. To elucidate the cellular processes underlying scar formation, here we perform unbiased single-cell mRNA sequencing of interstitial cells isolated from infarcted mouse hearts carrying a genetic tracer that labels epicardial-derived cells. Sixteen interstitial cell clusters are revealed, five of which were of epicardial origin. Focusing on stromal cells, we define 11 sub-clusters, including diverse cell states of epicardial- and endocardial-derived fibroblasts. Comparing transcript profiles from post-infarction hearts in C57BL/6J and 129S1/SvImJ inbred mice, which displays a marked divergence in the frequency of cardiac rupture, uncovers an early increase in activated myofibroblasts, enhanced collagen deposition, and persistent acute phase response in 129S1/SvImJ mouse hearts, defining a crucial time window of pathological remodeling that predicts disease outcome. : Using single-cell transcriptional profiling of mouse hearts carrying a reporter for epicardial-derived cells, Forte et al. provide a dynamic view of cardiac interstitial responses across acute and chronic phases of remodeling post-infarction. Comparing responses on diverse genetic backgrounds reveals novel cellular and transcriptional features of cardiac rupture propensity. Keywords: myocardial infarction, single-cell biology, cardiac rupture, fibrosis, genetic diversity, heart, mouse, epicardial-derived, scRNAseq, Seurat |
url |
http://www.sciencedirect.com/science/article/pii/S2211124720301625 |
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