Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice.

Cell Reports
Elvira ForteMilena B Furtado

Abstract

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.

Associated Datasets

Mar 4, 2020·Elvira Forte, Dan Skelly

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Citations

Sep 5, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Anis HannaNikolaos G Frangogiannis
Jul 8, 2020·International Journal of Molecular Sciences·Olga Bondareva, Bilal N Sheikh
Sep 18, 2020·Cardiovascular Research·Galen T SquiersAlexander R Pinto
Dec 29, 2020·Cellular Signalling·Alexandra M GarvinTaben M Hale
Nov 13, 2020·Journal of Molecular and Cellular Cardiology·Alexandra M Garvin, Taben M Hale
Feb 11, 2021·International Journal of Molecular Sciences·Lejla MedzikovicVivian de Waard
Mar 7, 2021·International Journal of Molecular Sciences·Elvira ForteNadia A Rosenthal
Mar 6, 2021·Trends in Cardiovascular Medicine·Irene V van BloklandPim van der Harst
Nov 8, 2020·Cellular Signalling·Anis HannaNikolaos G Frangogiannis
Apr 30, 2021·Frontiers in Physiology·Maria Cimini, Raj Kishore
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Ernesto Marín-SedeñoAdrián Ruiz-Villalba
Jul 3, 2021·Seminars in Cell & Developmental Biology·Taketaro Sadahiro, Masaki Ieda
Jul 24, 2021·Cell·Maksim V PlikusValerie Horsley
Jun 8, 2021·Physiological Genomics·Uchenna EmechebeAnthony P Barnes
Mar 24, 2021·Cardiovascular Research·E L RobinsonUNKNOWN EU-CardioRNA COST Action CA17129
Aug 12, 2021·Npj Regenerative Medicine·Rita N GomesDiana S Nascimento
Aug 28, 2021·International Journal of Molecular Sciences·Gang LiYuchen Yang
Aug 24, 2021·Circulation Research·Shijie LiuJames F Martin

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Datasets Mentioned

BETA
E-MTAB-7895

Methods Mentioned

BETA
scRNA-seq
RNA-Seq
enzymatic dissociation
flow
scRNAseq
transgenic
flow cytometry
FCS
chip
Illumina sequencing

Software Mentioned

Excel
MASTcpmDetRate
Ingenuity Pathway Analysis ( QIAGEN )
DoubletFinder
PANTHER Reactome
Harmony R
GraphPad Prism
Panther
CellRanger
MAST

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