Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dual roles of dermal adipogenesis in initiating and resolving neutrophilic skin inflammation

ABSTRACT: Dermal white adipose tissue (dWAT) is highly plastic and pivotal in host defense; however, its role in controlling neutrophil function remains unstudied. Here we found that Imiquimod-induced psoriatic skin inflammation prompted a dermal adipogenesis response, with preadipocyte expansion followed by differentiation into adipocytes. By single-cell RNAseq of the imiquimod skin samples, we found that dWAT was the primary site for initial neutrophil influx and activation, facilitated by interactions between neutrophils and preadipocytes via the IL1β-IL1R and CXCL1-CXCR2 pathways. IL1β-activated preadipocytes secreted CXCL1 and SAA3 to boost neutrophilic inflammation. Prolonged inflammation in preadipocytes led to their differentiation into early adipocytes, secreting anti-inflammatory lipids to resolve neutrophilic inflammation and restore homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE238086 | GEO | 2025/07/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Keratinocyte Wnt5β promotes dermal adipogenesis by simultaneously regulating adipocyte precursor cell conversion and adipogenic signaling

Project description:Skin is the largest organ in the body and comprises several types of cells. The intercellular plasticity of keratinocytes, fibroblasts, and skin adipocytes contributes to wound healing and dermal adipogenesis. Although keratinocyte activates dermal adipose tissue (dWAT) differentiation upon hair follicular cycle, regulating dWAT hyperplasia through keratinocyte reprogramming is still unknown. We used the CRISPR/Cas9 base editor to induce single nucleotide polymorphisms in Forkhead-box N1 (Foxn1) and identified the p.L19M variant that induced the formation of a thicker dWAT regardless of hair follicular cycle or wound healing. Foxn1 p.L19M activates Wnt5β through transcriptional activity. Wnt5β signaling induces the conversion of dWAT dermal fibroblasts into adipose precursor cells (APCs) and promotes APC adipocyte differentiation through keratinocyte epithelial-mesenchymal transition (EMT) and adipogenic signaling. Wnt5β is involved in the entire process of dWAT hyperplasia through APC supply and adipogenic signaling as a single factor. Foxn1 p.L19M and Wnt5β are expressed in keratinocytes, and a keratinocyte-derived adipogenic signal is critical for dermal adipogenesis. In addition, transient expression of Foxn1 p.L19M or Wnt5β using adeno-associated virus reproduced dermal adipocyte hyperplasia in mice. Considering the increasing importance of dWAT in functions such as the immune response, wound healing, hair follicle growth, and temperature control, this finding has potential applications in skin regeneration

2023-08-05 | GSE239791 | GEO

ATF3 is a novel regulator of mouse neutrophil migration.

Project description:Expression of the activating transcription factor 3 (ATF3) gene is induced by Toll-like receptor (TLR) signaling. In turn, ATF3 protein inhibits the expression of various TLR-driven pro-inflammatory genes. Given its counter-regulatory role in diverse innate immune responses, we defined the effects of ATF3 on neutrophilic airway inflammation in mice. ATF3 deletion was associated with increased lipopolysaccharide (LPS)-driven airway epithelia production of CXCL1, but not CXCL2, findings concordant with a consensus ATF3-binding site identified solely in the Cxcl1 promoter. Unexpectedly, ATF3-deficient mice did not exhibit increased airway neutrophilia after LPS challenge. Bone marrow chimeras revealed a specific reduction in ATF3-/- neutrophil recruitment to wild type lungs. In vitro, ATF3-/- neutrophils exhibited a profound chemotaxis defect. Global gene expression analysis identified ablated Tiam2 expression in ATF3-/- neutrophils. TIAM2 regulates cellular motility by activating Rac1-mediated focal adhesion disassembly. Notably, ATF3-/- and ATF3-sufficient TIAM2 knockdown neutrophils, both lacking TIAM2, exhibited increased focal complex area, along with excessive CD11b-mediated F-actin polymerization. Together, our data describe a dichotomous role for ATF3-mediated regulation of neutrophilic responses: inhibition of neutrophil chemokine production, but promotion of neutrophil chemotaxis. Ly6G+ neutrophils were purified by magnetic beads from WT or ATF3 KO bone marrow and RNA was immediately isolated for global gene expression using microarrays.

2014-04-05 | E-GEOD-53973 | biostudies-arrayexpress

ATF3 is a novel regulator of mouse neutrophil migration.

2014-04-05 | GSE53973 | GEO

Transcriptome analysis of mice dermal white adipose tissue during aging

Project description:Dermal white adipose tissue (dWAT) is one of the peripheral tissues directly adjacent to hair follicle(HF) and acts as critical macroenvironmental niche of HF. dWAT directly contribute to HF aging by paracrine signals secretion. However, the altered interrelationship between dWAT and HF with aging has not been thoroughly understood

2021-11-03 | GSE134893 | GEO

Characterizing gene expression changes within the human hair follicle bulb driven by hepatocyte growth factor secreted by perifollicular fat

Project description:Dermal white adipose tissue (dWAT) has been linked to modulation of murine hair follicle growth and cycling, however no studies have characterized its effects upon human hair growth. Since HGF was detected as a dWAT secretion product in HF-dWAT co-culture, the aim of this study was to characterize changes in gene expression in human dissected hair follicles vs. follicles cultured with surrounding dermal fat treated with/without a neutralizing antibody to HGF. To this end, the hair matrix and pre-cortex in each condition was isolated using laser-capture microdissection and microarray was carried out on the amplified cDNA. We identified 593 genes differentially modulated owing to the dWAT-derived HGF i.e. 301 up-regulated genes and 292 down-regulated genes in the presence of dWAT-secreted HGF and vice versa when HGF is neutralized.

2023-05-29 | GSE151972 | GEO

¬The EGFR/ErbB inhibitor neratinib promotes apoptosis and clearance by airway macrophages

Project description:Dysregulated neutrophilic inflammation can be highly destructive in chronic inflammatory diseases due to prolonged neutrophil lifespan and continual release of histotoxic mediators in inflamed tissues. Inducing neutrophil apoptosis, an immunologically silent form of cell death, may be beneficial in these diseases, provided that the apoptotic neutrophils are efficiently cleared from the tissue. Our previous research identified ErbB inhibitors as able to induce neutrophil apoptosis and reduce neutrophilic inflammation both in vitro and in vivo (Rahman et al. 2019). Here we expand on that work using a clinical ErbB inhibitor, neratinib, which has the potential to be repurposed in inflammatory diseases. We show that neratinib reduces neutrophilic migration to an inflammatory site in zebrafish larvae. Neratinib upregulates efferocytosis and reduces the number of dead neutrophils in mouse models of acute, but not chronic, lung injury, suggesting the drug may have therapeutic benefits in acute inflammatory settings. Phosphoproteomics analysis of human neutrophils shows that neratinib modifies the phosphorylation of proteins regulating apoptosis, migration and efferocytosis. This work identifies a potential efficacious mechanism for neratinib in acute lung inflammation by upregulating the clearance of dead neutrophils, and examination of the neutrophil phosphoproteome gives insight into the mechanisms by which this may be occurring.

2022-07-22 | PXD035125 | Pride

Cytokine Signaling Co-opts the CREB/CRTC Pathway in Obesity

Project description:Obesity stimulates the infiltration of adipose tissue by innate immune cells, which in turn promote insulin resistance via the NFkB mediated induction of pro-inflammatory cytokines, which interfere with triglyceride metabolism. The cAMP responsive factor CREB has also been implicated in adipose tissue inflammation and insulin resistance, although the underlying mechanism is unclear. Here, we show that high fat diet (HFD) feeding triggers activation of the CREB cofactors CRTC2 and CRTC3, which bind to CREB and mediate induction of CXCL1 and other cytokine genes in cooperation with NFkB. HFD feeding reduced adipocyte C/EBPa expression in adipose, leading to decreases in the expression of Salt Inducible Kinase 2 (SIK2), which otherwise phosphorylates and sequesters CRTCs in the cytoplasm. Depletion of SIK2 in adipose led to dephosphorylation of CRTC2 and CRTC3 (CRTC2/3) and to the induction of CXCL1 and other cytokine genes in adipocytes. Indeed, CRTC2/3 were found to stimulate the expression of a subset of cellular genes cooperatively with NF-kB in adipocytes. Knockout of both CRTC2 and CRTC3 in adipose decreased the expression of CXCL1/2 and thereby reduced neutrophil and macrophage infiltration. As depletion of CXCL1/2, with neutralizing antiserum or by KO of the CXCL1 gene restored glucose tolerance and insulin sensitivity in the setting of diet induced obesity, our results demonstrate that NF-kB and CREB/CRTC pathways modulate adipose tissue function in part via cooperative effects on target gene expression.

2021-10-27 | GSE160597 | GEO

Transcriptomic profile of human preadipocyte treated by macrophages from adipose tissue

Project description:Obesity is characterized by a chronic auto-inflammation of the hypertrophied white adipose tissue (WAT) associated with metabolic and vascular complications. WAT of obese subjects produces inflammatory factors like cytokines (IL6, TNF-alpha) and chemokines (CCL2 and IL-8) originating mainly from the accumulated macrophages. WAT macrophages profoundly affect adipose cell biology leading in particular to the inflammation of the adipocytes and altered differentiation of their precursors, the pre-adipocytes. We previously showed that conditioned media from WAT macrophages (ATM CM) induced inflammation in human pre-adipocytes. We performed pangenomic cDNA microarrays analysis to compare gene expression profiles between control and ATM CM treated preadipocytes. By a functional analysis, we identified the biological themes that best characterized the proinflammatory preadipocytes. The most significantly overrepresented GO Cellular Component categories were "cytokine-cytokine receptor interaction" and "chemokine signaling pathway", emphasizing the importance of cytokine and chemokine production by the inflammatory preadipocyte. The chemokines acting in concert to recruit leukocytes in inflamed tissues, still need to be more precisely identified in human WAT. Thus, our data lead to the identification of new chemokines involved in attraction of immune cells in inflamed human WAT. The transcriptomic profile of human preadipocytes was compared to that of preadipocyes treated by macrophages isolated from human adipose tissue. Two-condition experiment,human control preadipocyte vs preadipocyte treated by macrophages from adipose tissue. 5 biological replicates (with a dye-swap design).

2013-03-22 | E-GEOD-28445 | biostudies-arrayexpress

Jmjd3-mediated H3K27me3 dynamics orchestrate brown fat cell fate transition and regulate white fat plasticity

Project description:We performed ChIP-seq to chart genome-wide maps of H3K27me3 in brown preadipocytes and mature brown adipocytes. We observed a subset of brown fat-specific genes, but not common fat genes or white fat-specific genes, possess the H3K27me3 mark in preadipocytes, and this mark is erased in mature adipocytes. H3K27me3 ChIP-seq in brown preadipocytes and mature adipocytes.

2015-12-31 | E-GEOD-55469 | biostudies-arrayexpress

Single-cell transcriptional profiles of BM, PB and lung neutrophils from naïve (C57BL/6J), AT3, and AT3-gcsf tumor-bearing mice

Project description:To determine the effect of tumor-bearing vs. host neutrophilic inflammation on reinforcement of lung neutrophil-specific immunosuppressive function, we performed single-cell RNA sequencing (scRNA-seq) on BM, PB and lung neutrophils isolated from naïve (C57BL/6J), AT3, and AT3-gcsf tumor-bearing mice.

2022-12-12 | GSE217595 | 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