Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Profibrotic subsets of SPP1+ macrophages and POSTN+ fibroblasts contribute to fibrotic scarring in acne keloidalis

ABSTRACT: Acne keloidalis (AK) is a primary scarring alopecia characterized by longstanding inflammation in the scalp leading to keloid-like scar formation and hair loss. Histologically, AK is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in later stages. To further explore its pathogenesis, bulk RNA-sequencing and single-cell RNA sequencing were applied to scalp biopsy specimens of lesional and adjacent non-lesional skin in patients with clinically active disease. Unbiased clustering revealed 18 distinct cell populations, including two notable populations, POSTN+ fibroblasts with enriched extracellular matrix signatures, and SPP1+ myeloid cells M2 macrophages. Cell communication analyses indicate that fibroblasts and myeloid cells communicate by collagen and SPP1 signaling networks in lesional skin. Tissue immunofluorescence staining demonstrated SPP1+ myeloid cells and POSTN+ fibroblasts at the upper segment of outer root sheath of the hair follicle in the subacute stage, confirming micro-anatomic specificity with relevant disease activity. Therapy with intralesional corticosteroids reduced SPP1 and POSTN expression, and lessened AK progression. In summary, the communication between POSTN+ fibroblasts and SPP1+ myeloid cells by collagen and SPP1 axis may contribute to the pathogenesis of AK.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206790 | GEO | 2024/04/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Extensive alopecia areata is reversed by IL-23 cytokine antagonism

Project description:Alopecia areata (AA) is a prevalent disease associated with major emotional distress, and lacks effective, safe therapeutics for patients with extensive hair loss. This is the first report of hair regrowth with specific cytokine antagonism, in three patients with extensive hair loss ranging from 40% scalp involvement to alopecia universalis. Ustekinumab, an IL-12/23p40 antagonist that is highly effective in psoriasis, showed impressive ability to induce hair regrowth, coupled with suppression of inflammatory pathways and upregulation of hair keratins. Our report suggests that extensive AA is reversible using targeted treatments, opening the door for specific cytokine antagonism for this debilitating disease. We evaluated hair regrowth in three AA patients at 20 weeks after treatment with 3 subcutaneous doses of 90mg ustekinumab given at weeks 0, 4, and 16. Skin biopsies of lesional and non-lesional scalp (when available) were taken at baseline (week 0) and at week 20. We also obtained biopsies from three healthy individuals.

2015-12-08 | E-GEOD-74761 | biostudies-arrayexpress

Expression profiling of lesional and non-lesional bulge cells from Lichen planopilaris patients

Project description:Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. Whilst destruction of epithelial hair follicle stem cells (eHFSCs) that reside in an immunologically protected niche of the HF epithelium, the bulge, is a likely key event in LPP pathogenesis, this remains to be demonstrated. Laser capture microdissection of bulge cells from biopsies of lesional and non-lesional scalp skin from adult LPP patients were analyzed by microarray analysis.

2013-07-04 | E-MEXP-3859 | biostudies-arrayexpress

Plucked hair follicles from patients with chronic discoid lupus erythematosus show a disease-specific molecular signature

Project description:When faced with clinical symptoms of scarring alopecia – the standard diagnostic pathway involves a scalp biopsy which is an invasive and expensive procedure. Furthermore, clinical activity of scarring alopecias is often difficult to assess as symptoms of permanent damage and signs of activity can overlap or be difficult to distinguish. Here we report that gene expression analysis of only a small number of hair follicles (HF) plucked from lesional areas of the scalp is sufficient to characterise chronic discoid lupus erythematosus (CDLE). Lesional and non-lesional HFs were extracted from the scalp of patients with CDLE, psoriasis and healthy controls. The expression profile from CDLE HFs coincides with published profiles of CDLE from skin biopsy and was consistent with histopathological diagnostic features of CDLE. We therefore propose that information obtained from this non-invasive approach are sufficient to diagnose scalp LE.

2018-10-31 | GSE119207 | GEO

JAK3/TEC and TYK2/JAK1 inhibitors demonstrate significant improvement in scalp alopecia areata biomarkers

Project description:We present the biopsy sub-study results from the first randomized, placebo-controlled clinical trial in patients with alopecia areata (AA) with ≥50% scalp hair loss and ≤7 years since the last AA episode. In this sub-study, we evaluated the molecular responses to PF-06651600, an oral inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, and PF-06700841, an oral TYK2/JAK1 inhibitor, versus placebo in nonlesional and lesional scalp biopsies of biopsy samples from patients with AA.

2022-01-25 | GSE148346 | GEO

Genetic lineage tracing defines myofibroblast origin and function in the injured heart

Project description:Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell-type in terms of their origins and functional effects in vivo. Methods: Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen inducible Cre for cellular lineage tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Results: Lineage tracing with 4 additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin+ myofibroblasts reduces collagen production and scar formation after myocardial infarction. Periostin-traced myofibroblasts also revert back to a less activated state upon injury resolution. Conclusions: Our results define the myofibroblast as a periostin-expressing cell-type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21+ tissue-resident fibroblasts. Fluidigm C1 whole genome transcriptome analysis of lineage mapped cardiac myofibroblasts

2016-06-14 | E-GEOD-83337 | biostudies-arrayexpress

Fibroblast SPP1 mediates ECM deposition and inhibits SMC contractility in MFS aortic aneurysm

Project description:Mutations in the Fbn1 gene cause Marfan Syndrome (MFS) and are associated with excessive transforming growth factor beta (TGF-β) signalling activation, which contributes to extracellular matrix (ECM) homeostasis disruption, thoracic aortic aneurysm (TAA) and dissection development. In this study, we aimed to explore the underlying events contributing to ECM metabolism imbalance and TAA and dissection formation in MFS. We performed sequencing analysis and investigated differentially expressed genes as well as cellular communication using CellChat. Fourteen ECM-related differentially expressed genes (DEGs) were identified. Among the 14 genes, secreted phosphoprotein 1 (Spp1) was involved in multiple pathological processes. We then stimulated primary mouse perivascular fibroblasts and aortic SMCs with recombinant Spp1 and recorded increased collagen expression in fibroblasts and decreased expression of Acta2 and Tagln in SMCs. We also investigated SPP1 levels in healthy controls and patients with TAA and found that elevated SPP1 levels were associated with an increased risk of TAA. Our results have indicated that Spp1 regulates ECM changes in fibroblasts and SMCs contractility during TAA. We believe that our study makes a significant contribution to the literature because our results suggest that Spp1 may serve as a potential target for TAA treatment.

2024-12-12 | GSE190720 | GEO

Molecular and cellular profilling of scalp psoriasis reveals differences and similarities compared to skin psoriasis

Project description:Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis on other skin areas. We sought to determine the cellular and mollecular phenotype of scalp psoriasis by performing a comparative analysis of scalp vs skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement, and 10 control subjects without psoriasis. Our results suggest that even in the scalp psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprinting were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with skin psoriasis which was mainly associated with activation of TNFâµ/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes. To define the transcriptomic profile of scalp skin, punch biopsies (6 mm diameter) were obtained from 20 Caucasian patients with untreated moderate to severe psoriasis with significative scalp involvement and 10 control subjects without psoriasis (N). Lesional (LS) samples were isolated from the infiltrated border of a plaque of psoriasis. Non lesional (NL) samples were taken from scalp areas with no visible psoriasis between the infiltrated plaques.

2015-11-25 | E-GEOD-75343 | biostudies-arrayexpress

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Project description:Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. Thus, we performed single-cell transcriptomic profiling of 28,695 lesional and non-lesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted towards a cancer-associated fibroblast (CAF)-like phenotype, with POSTN+WNT5A+ CAFs increased in PN, and similarly so in squamous cell carcinoma. A multi-center cohort study revealed an increased risk of SCC and CAF-associated malignancies (breast and colorectal) in PN patients. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in PN patients. Ligand receptor analyses demonstrated a fibroblast neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV. Compared to atopic dermatitis and psoriasis, mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype. These findings identify a pathogenic and targetable POSTN+WNT5A+ fibroblast subpopulation that may predispose CAF-associated malignancies in PN patients.

2024-01-22 | GSE233280 | GEO

Genetic lineage tracing defines myofibroblast origin and function in the injured heart

2016-06-14 | GSE83337 | GEO

Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia

Project description:Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet the mechanisms for decreased hair growth in this disorder are unclear. Here, we show that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. During normal follicle cycling in mice Ptgds and PGD2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein-coupled receptor 44 (GPR44), but not the prostaglandin D2 receptor 1(PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment. 5 individuals with Androgenetic Alopecia were biopsied at both their haired and bald scalp for mRNA purification and microarray (total 10 arrays)

2012-03-26 | E-GEOD-36169 | biostudies-arrayexpress

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