Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cardiac fibroblasts regulate macrophage ontogeny, phenotype and function during cardiac injury

ABSTRACT: Cardiac fibroblasts regulate macrophage ontogeny, phenotype and function during cardiac injury

PROVIDER: PRJNA487063 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Cardiac fibroblasts regulate macrophage ontogeny, phenotype and function during cardiac injury

Project description:Two types of monocytes, inflammatory and patrolling, infiltrate the hearts in both human myocarditis and murine experimental autoimmune myocarditis (EAM) model. The fates and functions of these infiltrating monocytes governing the progression of heart failure remain unclear. Here, we created parabiotic EAM and naïve mice to show that cardiac inflammation facilitate monocyte-to-macrophage differentiation. Using a combination of flow cytometry, time lapsed imaging and transmission electron microscopy, we demonstrated in vitro that cardiac fibroblasts interact with monocytes and are instrumental in facilitating monocyte-to-macrophage differentiation. Moreover, IL-17A stimulated cardiac fibroblasts completely arrested Ly6Clo monocyte proliferation and inhibited both Ly6Chi and Ly6Clo monocyte-to-macrophage differentiation both in vitro and in vivo after intracardiac injections of monocytes into the hearts. Intriguingly, IL-17A signaling through cardiac fibroblasts also significantly downregulated Mer tyrosine kinase (MerTK) expressions on Ly6Chi monocyte-derived macrophages, thus jeopardizing their phagocytic abilities. Collectively, our results implicate divergent fates and functions of heart-infiltrating monocytes influenced by cardiac fibroblasts.

2021-08-01 | GSE118861 | GEO

Cytokine–ontogeny interaction shapes macrophage transcriptional states

Project description:Cytokine–ontogeny interaction shapes macrophage transcriptional states

| PRJNA1303100 | ENA

Cytokine–ontogeny interaction shapes macrophage transcriptional states

Project description:Macrophage ontogeny and local cytokines jointly govern tumor-associated macrophage behaviour, yet how these signals integrate to generate pro- or antitumor outputs is unknown. Here, we apply a reductionist, multi-scale pipeline to systematically map eight reference macrophage states generated by ex vivo differentiation of mouse bone marrow cells with macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF) and subsequent cytokine polarization (IFN-gamma, IL-4, IL-10, TGF-beta). We integrated transcriptomic, 3D spheroid, and in vivo metastatic analyses to discover a lineage dependent polarity switch: IL-4 drives an ARG1+, tumor-supportive programme in M-CSF macrophages but, via NfkB, induces a CCR7+ inflammatory phenotype in GM-CSF macrophages. IFN-gamma uniformly activates STAT1/IRF pathways, maintaining antitumor profiles, whereas IL-10 and TGF-beta maximally evoke SPP1+ immunosuppressive signatures after GM-CSF priming. Functional assays confirmed these transcriptional states dictate opposite effects on tumor growth, invasion, and pulmonary metastasis. Integration of all parameters yielded an "ontogeny cytokine code" that predicts macrophage function based on developmental history and cytokine milieu. Identifying CSF-defined lineage as a master regulator of macrophage heterogeneity provides a blueprint for precision immunotherapies that reprogram macrophages in solid tumors. This SuperSeries is composed of the SubSeries listed below.

2025-09-30 | GSE304868 | GEO

Cytokine–ontogeny interaction shapes macrophage transcriptional states (combined GM-CSF– and M-CSF–derived macrophages)

Project description:We generated eight macrophage states using a cytokine–ontogeny matrix, combining two macrophage ontogenies (M-CSF and GM-CSF) with four cytokines (IL‑4, IFN‑γ, IL‑10, TGF‑β). Bulk RNA‑seq on five biological replicates per condition revealed that PC1 (54% variance) segregated ontogeny: GM‑CSF states loaded negatively, M‑CSF states positively. Gene‑set enrichment analysis of negative PC1 loadings highlighted NfkB programs, confirming the intrinsic inflammatory bias of GM‑CSF macrophages (Hamilton 2008; Hamilton et al. 2016)

2025-09-30 | GSE304646 | GEO

Ageing-dependent cardiac macrophage gene expression change alters cardiac injury responses and ageing

Project description:Transcription profiling by array of Mrc1+ cardiac tissue macrophage subsets to identify deferentially expressed genes.

2014-08-04 | E-MTAB-2168 | biostudies-arrayexpress

Cytokine–ontogeny interaction shapes macrophage transcriptional states (GM-CSF–derived macrophages)

Project description:Cytokine–ontogeny interaction shapes macrophage transcriptional states (GM-CSF–derived macrophages)

| PRJNA1301994 | ENA

Cytokine–ontogeny interaction shapes macrophage transcriptional states (M-CSF–derived macrophages)

Project description:Cytokine–ontogeny interaction shapes macrophage transcriptional states (M-CSF–derived macrophages)

| PRJNA1301987 | ENA

Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis

Project description:Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis

| PRJNA986064 | ENA

Mitochondria regulate proliferation in adult cardiac myocytes

Project description:Mitochondria regulate proliferation in adult cardiac myocytes

| PRJNA1102406 | ENA

Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis

Project description:Scar tissue that forms in the heart after cardiac injury, comprises an abundant number of non-excitable fibroblasts in close proximity to excitable myocytes, that are embedded within the matrix of the scar. Electrical coupling of fibroblasts and myocytes is known to occur and in vitro simulation studies have demonstrated that changes in fibroblast membrane potential can lead to myocyte excitability and susceptibility to arrhythmogenesis. However, the physiologic significance of electrical coupling between myocytes and fibroblasts in scar tissue, in the regulation of cardiac excitability and arrhythmogenesis in vivo is hotly debated and has never been demonstrated. Here, we genetically engineer a mouse that expresses the optogenetic cationic channel ChR2 exclusively in cardiac fibroblasts and not in cardiac myocytes. We subject the animal to cardiac injury and demonstrate that optical stimulation of scar tissue elicits cardiac excitability and induces arrhythmias. Connexin 43 (Cx43) is a gap junctional protein that is the most abundant connexin isoform in the heart and thought to mediate electrical coupling of fibroblasts and myocytes. Using genetic loss of function approaches, we show that Cx43 is not necessary for fibroblast-myocyte electrical coupling in vivo. CRISPR/Cas 9 mediated sequential deletion of the other highly expressed connexins also did not affect electrical coupling of fibroblasts and myocytes. Using computational modeling approaches, we show that gap junctional and non-gap junctional coupling mechanisms synergize in a functionally redundant manner to excite myocytes coupled to fibroblasts. These observations demonstrate that cardiac fibroblasts in scar tissue directly regulate cardiac excitability in vivo and can induce arrhythmogenesis. Our findings throw insight into the importance of electrical coupling of fibroblasts and myocytes in the genesis of scar associated cardiac arrhythmias.

2023-09-28 | GSE235434 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data