Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell analysis of Tgfbr2-KO pulmonary monocytes and interstitial macrophages

ABSTRACT: Lung interstitial macrophages (IMs) inhabit the lung parenchyma and are thought to contribute to lung immunoregulation and homeostasis. While recent progress has been made about the development, diversity and transcriptional regulation of lung IMs, the microenvironmental signals responsible for their tissue-specific identity remain unidentified. Here we found, in mice, that lung endothelial cell-derived Tgf 1 specifically triggered a core Tgf receptor-dependent lung IM signature in bone marrow-derived monocytes and macrophages (Macs). In vivo, myeloid-specific ablation of Tgf receptor signaling severely impaired monocyte-to-IM development, resulting in the accumulation of perivascular monocytes, decreased IM numbers and a severe loss of IM-intrinsic identity. Of note, monocyte-to-IM development was similarly impaired in the absence of endothelial-specific Tgf 1. Functionally, mice selectively lacking Tgf receptor in IMs exhibited a severe impairment of the lung immunoregulatory environment and prematurely developed lung hyperinflation, increased compliance and decreased elastance, changes classically associated with ageing. Our work identifies a novel endothelial - IM axis involving Tgf 1-Tgf r interactions that shapes IM identity and thereby sustains lung tissue integrity, thus providing foundations for IM-targeted interventions in the context of lung ageing and other chronic inflammatory disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE285104 | GEO | 2025/03/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Endothelial Tgfß1 supports lung interstitial macrophage differentiation and pulmonary homeostasis

Project description:Lung interstitial macrophages (IMs) inhabit the lung parenchyma and are thought to contribute to lung immunoregulation and homeostasis. While recent progress has been made about the development, diversity and transcriptional regulation of lung IMs, the microenvironmental signals responsible for their tissue-specific identity remain unidentified. Here we found, in mice, that lung endothelial cell-derived Tgf 1 specifically triggered a core Tgf receptor-dependent lung IM signature in bone marrow-derived monocytes and macrophages (Macs). In vivo, myeloid-specific ablation of Tgf receptor signaling severely impaired monocyte-to-IM development, resulting in the accumulation of perivascular monocytes, decreased IM numbers and a severe loss of IM-intrinsic identity. Of note, monocyte-to-IM development was similarly impaired in the absence of endothelial-specific Tgf 1. Functionally, mice selectively lacking Tgf receptor in IMs exhibited a severe impairment of the lung immunoregulatory environment and prematurely developed lung hyperinflation, increased compliance and decreased elastance, changes classically associated with ageing. Our work identifies a novel endothelial - IM axis involving Tgf 1-Tgf r interactions that shapes IM identity and thereby sustains lung tissue integrity, thus providing foundations for IM-targeted interventions in the context of lung ageing and other chronic inflammatory disorders.

2025-03-10 | GSE271467 | GEO

Interstitial Macrophage Phenotypes in Schistosoma-Induced Pulmonary Hypertension

Project description:Schistosomiasis, a prevalent cause of pulmonary hypertension (PH) globally, triggers type 2 inflammation, with interstitial macrophages (IMs) derived from monocytes playing a crucial role. These IMs produce thrombospondin-1 (TSP-1), activating TGF-β and driving PH pathology. Two distinct IM subpopulations were identified: resident FOLR2+ IMs expressing monocyte recruitment factors, and recruited CCR2+ IMs expressing TSP-1. Upon exposure to Schistosoma, the CCR2+ subpopulation expanded. Flow cytometry and single-cell RNA sequencing confirmed these findings, revealing crosstalk between IM subpopulations. The resident FOLR2+ IMs increased expression of monocyte recruitment ligands, while the recruited CCR2+ IMs expressed elevated TSP-1, activating TGF-β and contributing to PH. This study provides insights into the complex interplay of IM subpopulations in Schistosoma-induced PH, shedding light on potential therapeutic targets for this global health concern.

2024-05-08 | GSE254338 | GEO

Single-cell RNAseq analysis (10X Genomics Chromium) of refilled lung interstium macrophages at the time points of 12h, 24h and 48h after depletion

Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. The lung IMs and monocytes from the mice at 12 hours (DT12h), 24 hours (DT24h) and 48 hours (DT48h) after diphtheria toxin (DT)-induced IM depletion were analyzed and compared using single-cell RNA sequencing. A subpopulation was found to be a transit differentiating cells from monocytes to IMs. Transcription factor activity analysis and trajectory showed cMAF and MAFb transcription factors played important roles in monocyte-IM differentiation.

2023-02-07 | GSE193896 | GEO

Murine Pulmonary Interstitial Macrophage Subsets after Lipopolysaccharide

Project description:We sought to characterize pulmonary interstitial macrophage (IM) origin, subsets, and transcriptomic profiles during homeostasis and lipopolysaccharide (LPS) induced acute lung inflammation. During homeostasis, we used three complementary methods: spectral flow cytometry, single-cell RNA-sequencing, and gene regulatory network enrichment to demonstrate that IMs can be divided into two core subsets distinguished by surface and transcriptional expression of folate receptor β (Folr2/FRβ). Within FRβ+ IMs we identified a subpopulation marked by co-expression of LYVE1. During acute LPS-induced inflammation, lung IM numbers expand. Lineage tracing revealed IM expansion was due to recruitment of monocyte-derived IMs. At the peak of inflammation, recruited IMs were comprised of two unique subsets defined by expression of genes associated with interferon signaling and glycolytic pathways. As recruited IMs matured, they adopted the overall transcriptional state of FRβ- resident IMs but retained expression in several origin-specific genes. FRβ+ IMs were of near-pure resident origin.

2023-03-17 | GSE218884 | GEO

Single-cell RNAseq analysis (10X Genomics Chromium) of cMAF- and Mafb-deficent lung monocytes and interstium macrophages

Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. The lung IMs and monocytes from either Lyz2-Cre Mafflox/flox mice (cMAF-KO), Lyz2-Cre Mafbflox/flox (MAFb-KO), Lyz2-Cre Mafflox/flox Mafbflox/flox (dKO) or control litermate mice without floxp locus (Control) were analyzed and compared using single-cell RNA sequencing. All the main substs, i.e. Ly6C+ classical monocytes, Ly6C- patrolling monocytes, CD206+ IMs, CD206- IMs were found in control sample, while IMs are absent in both MAFb-KO and dKO sample accompied by a new intermediate population independent of Mafb expression. CMAF-KO sample show less impact in cell population composition with a lower freqency of CD206+ IM population.

2023-02-07 | GSE193891 | GEO

Two distinct interstitial macrophage populations coexist across tissues in unique subtissular niches [FACs sorted]

Project description:Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation and in multiple pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within tissue parenchyma remain poorly defined. Here, we studied IMs from murine lung, fat, heart and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localisation. Using a mouse model of inducible macrophage depletion (SLCO2B1-DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs exist across tissues and exhibit conserved niche-dependent functional programming.

2019-01-26 | GSE125667 | GEO

Two distinct interstitial macrophage populations coexist across tissues in unique subtissular niches [lung interstitial]

2019-01-26 | GSE125676 | GEO

Single-cell RNAseq analysis (10X Genomics Chromium) of refilled lung interstium macrophages on day 4 after depletion

Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. The IMs in Day 4 post-depletion were compared to the those without depletion. Results showed that refilled IMs had a lower ratio of CD206+ IM vs CD206- subpopulation comparing to IMs without depletion, but they shared high similarity to each other, indicating that the de novo IM population had been established before Day 4 post-depletion.

2023-02-07 | GSE193894 | GEO

Coordinated chemokine expression defines macrophage subsets across tissues [scRNA-seq: hSk]

Project description:Lung-resident macrophages, which include alveolar macrophages and interstitial macrophages (IMs), exhibit a high degree of diversity, generally attributed to different activation states, and often complicated by the influx of monocytes into the pool of tissue-resident macrophages. To gain a deeper insight into the functional diversity of IMs, here we perform comprehensive transcriptional profiling of resident IMs and reveal ten distinct chemokine-expressing IM subsets at steady state and during inflammation. Similar IM subsets that exhibited coordinated chemokine signatures and differentially expressed genes were observed across various tissues and species, indicating conserved specialized functional roles. Other macrophage types shared specific IM chemokine profiles, while also presenting their own unique chemokine signatures. Depletion of CD206hi IMs in Pf4creR26EYFP+DTR and Pf4creR26EYFPCx3cr1DTR mice led to diminished inflammatory cell recruitment, reduced tertiary lymphoid structure formation and fewer germinal center B cells in models of allergen- and infection-driven inflammation. These observations highlight the specialized roles of IMs, defined by their coordinated chemokine production, in regulating immune cell influx and organizing tertiary lymphoid tissue architecture.

2023-03-03 | GSE225662 | GEO

Coordinated chemokine expression defines macrophage subsets across tissues

Project description:This SuperSeries is composed of the SubSeries listed below. Lung-resident macrophages, which include alveolar macrophages and interstitial macrophages (IMs), exhibit a high degree of diversity, generally attributed to different activation states, and often complicated by the influx of monocytes into the pool of tissue-resident macrophages. To gain a deeper insight into the functional diversity of IMs, here we perform comprehensive transcriptional profiling of resident IMs and reveal ten distinct chemokine-expressing IM subsets at steady state and during inflammation. Similar IM subsets that exhibited coordinated chemokine signatures and differentially expressed genes were observed across various tissues and species, indicating conserved specialized functional roles. Other macrophage types shared specific IM chemokine profiles, while also presenting their own unique chemokine signatures. Depletion of CD206hi IMs in Pf4creR26EYFP+DTR and Pf4creR26EYFPCx3cr1DTR mice led to diminished inflammatory cell recruitment, reduced tertiary lymphoid structure formation and fewer germinal center B cells in models of allergen- and infection-driven inflammation. These observations highlight the specialized roles of IMs, defined by their coordinated chemokine production, in regulating immune cell influx and organizing tertiary lymphoid tissue architecture.

2023-03-02 | GSE225668 | 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