Spatially Conserved CD248⁺ FAP⁺ Fibroblasts Drive Post‑ Infarction Cardiac Fibrosis Through an Inflammation‑ Amplifying Niche
Abstract
Myocardial infarction (MI) triggers a maladaptive fibrotic response that leads to heart failure, yet the cellular drivers of this process remain incompletely understood. Here we integrate single cell RNA‑ sequencing (scRNA‑ seq) data from mouse hearts after MI (5,077 cells) to map the cellular landscape of post‑ infarction fibrosis. We identify a previously uncharacterized fibroblast subset, designated CF1 (conserved fibroblast 1), characterized by high expression of Cd248, Fap, Cthrc1, and Postn. CF1 cells constitute 229 cells and are markedly enriched in infarcted hearts. Differential expression analysis reveals 393 genes upregulated in CF1 compared to other fibroblasts, with functional enrichment pointing to extracellular matrix organization, inflammatory response, and TGF‑ β signaling. Notably, the CF1 transcriptional signature is also detected in publicly available datasets of liver, kidney, and lung fibrosis, suggesting a conserved pro‑ fibrotic program across organs. Our findings uncover a previously unappreciated fibroblast subset that may serve as a central hub for inflammation‑ driven matrix remodeling after MI, providing potential diagnostic and therapeutic targets for post‑ infarction heart failure.
References
1.Roth,G.A.etal.Globalburdenofcardiovasculardiseasesandriskfactors,1990–2019:updatefromtheGBD2019study.J.Am.Coll.Cardiol.76,2982–3021(2020).
2.Benjamin,E.J.etal.Heartdiseaseandstrokestatistics—2019update:areportfromthe AmericanHeartAssociation.Circulation139,e56–e528(2019).
3.Prabhu,S.D.&Frangogiannis,N.G.Thebiologicalbasisforcardiacrepairaftermyocardial infarction:frominflammationtofibrosis.Circ.Res.119,91–112(2016).
4.Talman,V.&Ruskoaho,H.Cardiacfibrosisinmyocardialinfarction—fromrepairtoremodeling.CellTissueRes.365,563–581(2016).
5.Travers,J.G.,Kamal,F.A.,Robbins,J.,Yutzey,K.E.&Blaxall,B.C.Cardiacfibrosis:thefibroblast awakens.Circ.Res.118,1021–1040(2016).
6.Forte,E.etal.Spatialtranscriptomicsrevealsadynamicborderzoneduringmyocardial infarction.Circ.Res.130,1234–1250(2022).
7.Kuppe,C.etal.Decodingmyofibroblastoriginsinhumankidneyfibrosis.Nature589,281–286(2021).
8.Ruiz‑Villalba,A.etal.Spatialandsingle‑celltranscriptomicsofthemouseheartafter myocardialinfarction.Sci.Data13,45(2026).
9.Amrute,J.M.etal.Targetingimmune–fibroblastcellcommunicationinheartfailure.Nature 635,423–433(2024).
10.Li,Y.etal.CD248+fibroblastspromotepost‑infarctioncardiacfibrosisthroughACKR3‑mediatedT‑cellrecruitment.Nat.Cardiovasc.Res.4,256–272(2025).
11.Lavine,K.J.etal.Single‑cellanalysisrevealsaFAP+POSTN+fibroblastsubsetthatdrives cardiacfibrosisviaIL‑1βsignaling.Nature634,123–131(2024).
12.Frangogiannis,N.G.Transforminggrowthfactor‑βintissuefibrosis.J.Exp.Med.217,e20190103(2020).
13.Dinarello,C.A.Interleukin‑1inthepathogenesisandtreatmentofinflammatorydiseases.Blood117,3720–3732(2011).
---
Metrics
DOI:
Submission ID:
Downloads
Posted
How to Cite
Declaration of Competing Interests
The authors declare no competing interests to disclose.
Copyright
The copyright holder for this preprint is the author/funder.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.