Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Role of bulge epidermal stem cells and TSLP signaling

ABSTRACT: Psoriasis is a common inflammatory skin disease involving a cross-talk between epidermal and immune cells. The role of specific epidermal stem cell populations, including hair follicle stem cells (HF-SCs) in psoriasis is not well defined. Here we show reduced expression of c-JUN and JUNB in bulge HF-SCs in patients with scalp psoriasis. Using lineage tracing in mouse models of skin inflammation with inducible deletion of c-Jun and JunB, we found that mutant bulge HF-SCs initiate epidermal hyperplasia and skin inflammation. Mechanistically, Thymic Stromal Lymphopoietin (TSLP) was identified in mutant cells as a paracrine factor stimulating proliferation of neighboring non-mutant epidermal cells, while mutant inter-follicular epidermal (IFE) cells are lost over time. Blocking TSLP in psoriasis-like mice reduced skin inflammation and decreased epidermal proliferation, VEGF? expression and STAT5 activation. These findings unravel a distinct role of HF-SCs and IFE cells in inflammatory skin disease and provide novel mechanistic insights into epidermal cell interactions in inflammation.

SUBMITTER: Dr. Nuria Gago-Lopez

PROVIDER: S-SCDT-EMM-2019-10697 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Role of bulge epidermal stem cells and TSLP signaling in psoriasis.

Project description:Psoriasis is a common inflammatory skin disease involving a cross-talk between epidermal and immune cells. The role of specific epidermal stem cell populations, including hair follicle stem cells (HF-SCs) in psoriasis is not well defined. Here, we show reduced expression of c-JUN and JUNB in bulge HF-SCs in patients with scalp psoriasis. Using lineage tracing in mouse models of skin inflammation with inducible deletion of c-Jun and JunB, we found that mutant bulge HF-SCs initiate epidermal hyperplasia and skin inflammation. Mechanistically, thymic stromal lymphopoietin (TSLP) was identified in mutant cells as a paracrine factor stimulating proliferation of neighboring non-mutant epidermal cells, while mutant inter-follicular epidermal (IFE) cells are lost over time. Blocking TSLP in psoriasis-like mice reduced skin inflammation and decreased epidermal proliferation, VEGFα expression, and STAT5 activation. These findings unravel distinct roles of HF-SCs and IFE cells in inflammatory skin disease and provide novel mechanistic insights into epidermal cell interactions in inflammation.

| S-EPMC6835205 | biostudies-literature

Genetically induced cell death in bulge stem cells reveals their redundancy for hair and epidermal regeneration.

Project description:Adult mammalian epidermis contains multiple stem cell populations in which quiescent and more proliferative stem and progenitor populations coexist. However, the precise interrelation of these populations in homeostasis remains unclear. Here, we blocked the contribution of quiescent keratin 19 (K19)-expressing bulge stem cells to hair follicle formation through genetic ablation of the essential histone methyltransferase Setd8 that is required for the maintenance of adult skin. Deletion of Setd8 eliminated the contribution of bulge cells to hair follicle regeneration through inhibition of cell division and induction of cell death, but the growth and morphology of hair follicles were unaffected. Furthermore, ablation of Setd8 in the hair follicle bulge blocked the contribution of K19-postive stem cells to wounded epidermis, but the wound healing process was unaltered. Our data indicate that quiescent bulge stem cells are dispensable for hair follicle regeneration and epidermal injury in the short term and support the hypothesis that quiescent and cycling stem cell populations are equipotent.

| S-EPMC4583782 | biostudies-literature

Notch signaling in bulge stem cells is not required for selection of hair follicle fate.

Project description:Notch signaling plays an important role in hair follicle maintenance, and it has been suggested that Notch is also required for follicular fate selection by adult hair follicle stem cells in the bulge. Here we demonstrate that, on the contrary, Notch signaling in bi-potential bulge stem cells or their uncommitted descendents acts to suppress the epidermal fate choice, thus ensuring follicular fate selection. To examine the role of Notch signaling in adult hair follicle stem cells, we used a Krt1-15-CrePR1 transgenic mouse line to delete Rbpj or all Notch proteins specifically in the bulge stem cells. We conclusively determined that in the absence of Notch signaling, bulge stem cell descendents retain their capacity to execute the follicular differentiation program but fail to maintain it owing to their genetic deficiency. The defect in terminal differentiation caused the diversion of Notch-deficient hair follicles to epidermal cysts, and the presence of wild-type cells could not prevent this conversion. Importantly, our analysis revealed that a functional Notch signaling pathway was required to block bulge stem cells from migrating into, and assuming the fate of, interfollicular epidermis. Taken together, our findings yield detailed insight into the function of Notch signaling in hair follicle stem cells and reveal the mechanism of the replacement of Notch-deficient adult hair follicles by epidermal cysts.

| S-EPMC2727555 | biostudies-literature

Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling.

Project description:The skin is a classical example of a tissue maintained by stem cells. However, the identity of the stem cells that maintain the interfollicular epidermis and the source of the signals that control their activity remain unclear. Using mouse lineage tracing and quantitative clonal analyses, we showed that the Wnt target gene Axin2 marks interfollicular epidermal stem cells. These Axin2-expressing cells constitute the majority of the basal epidermal layer, compete neutrally, and require Wnt/β-catenin signaling to proliferate. The same cells contribute robustly to wound healing, with no requirement for a quiescent stem cell subpopulation. By means of double-labeling RNA in situ hybridization in mice, we showed that the Axin2-expressing cells themselves produce Wnt signals as well as long-range secreted Wnt inhibitors, suggesting an autocrine mechanism of stem cell self-renewal.

| S-EPMC4081860 | biostudies-literature

Axin2 marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling.

Project description:How stem cells maintain their identity and potency as tissues change during growth is not well understood. In mammalian hair, it is unclear how hair follicle stem cells can enter an extended period of quiescence during the resting phase but retain stem cell potential and be subsequently activated for growth. Here, we use lineage tracing and gene expression mapping to show that the Wnt target gene Axin2 is constantly expressed throughout the hair cycle quiescent phase in outer bulge stem cells that produce their own Wnt signals. Ablating Wnt signaling in the bulge cells causes them to lose their stem cell potency to contribute to hair growth and undergo premature differentiation instead. Bulge cells express secreted Wnt inhibitors, including Dickkopf (Dkk) and secreted frizzled-related protein 1 (Sfrp1). However, the Dickkopf 3 (Dkk3) protein becomes localized to the Wnt-inactive inner bulge that contains differentiated cells. We find that Axin2 expression remains confined to the outer bulge, whereas Dkk3 continues to be localized to the inner bulge during the hair cycle growth phase. Our data suggest that autocrine Wnt signaling in the outer bulge maintains stem cell potency throughout hair cycle quiescence and growth, whereas paracrine Wnt inhibition of inner bulge cells reinforces differentiation.

| S-EPMC4801317 | biostudies-literature

Expression data from squamous cell carcinoma stem cells, epidermal progenitor cells and hair follicle bulge stem cells

2011-12-30 | GSE29328 | GEO

The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells.

Project description:Activation of Wnt/β-catenin signaling in adult mouse epidermis leads to expansion of the stem cell compartment and redirects keratinocytes in the interfollicular epidermis and sebaceous glands (SGs) to differentiate along the hair follicle (HF) lineages. Here we demonstrate that during epidermal development and homeostasis there is reciprocal activation of the androgen receptor (AR) and β-catenin in cells of the HF bulb. AR activation reduced β-catenin-dependent transcription, blocked β-catenin-induced induction of HF growth, and prevented β-catenin-mediated conversion of SGs into HFs. Conversely, AR inhibition enhanced the effects of β-catenin activation, promoting HF proliferation and differentiation, culminating in the formation of benign HF tumors and a complete loss of SG identity. We conclude that AR signaling has a key role in epidermal stem cell fate selection by modulating responses to β-catenin in adult mouse skin.

| S-EPMC4641324 | biostudies-literature

Expression data from squamous cell carcinoma stem cells, epidermal progenitor cells and hair follicle bulge stem cells

Project description:We used microarrays to assess the global gene expression profiles of cancer stem cells which were isolated from cutaneous squamous cell carcinomas which developed when WT, TGF beta receptor II ko, FAK KO, and TGF beta receptor II/FAK double KO were subjected to continuous DMBA treatment. Squamous cell carcinoma stem cells were compared to epidermal progenitor cells (CD49fhighCD34low) and hair follicle bulge stem cells (CD49fhighCD34high). Squamous cell carcinoma was initiated by continuous DMBA treatment (complete carcinogenesis). Cancer cells were sorted based on high CD29 and CD49f expression, infected with a retrovirus expressing a triple modality reporter (luciferase, RFP, thymidine kinase) and grafted onto nude recipient mice. RFP positive lineage was separated into CD29 high, CD49f high and CD34 low; or CD29high, CD49f high and CD34high squamous cell carcinoma initiating cells.

2011-12-30 | E-GEOD-29328 | biostudies-arrayexpress

Characterization and isolation of stem cell-enriched human hair follicle bulge cells.

Project description:The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hiCD24loCD34loCD71loCD146lo) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays.

| S-EPMC1323261 | biostudies-literature

Ablation of coactivator Med1 regulates bulge keratinocyte stem cells and accelerates epidermal regeneration after injury.

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-01-01 | GSE50673 | GEO