MiR-195-5p Regulates Hair Follicle Inductivity of Dermal Papilla Cells by Suppressing Wnt/β-catenin Activation
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ABSTRACT:
ORGANISM(S): Merkel cell polyomavirus Human alphaherpesvirus 2 Betapolyomavirus hominis Human alphaherpesvirus 1 Human gammaherpesvirus 8 JC polyomavirus Betapolyomavirus macacae Homo sapiens Human immunodeficiency virus 1 human gammaherpesvirus 4 Human betaherpesvirus 5
PROVIDER: GSE77825 | GEO | 2016/02/11
SECONDARY ACCESSION(S): PRJNA311680
REPOSITORIES: GEO
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Project description:Dermal papilla (DP) cells play a vital role in hair follicle (HF) development and postnatal hair cycling. However, the abilities are lost on further culture. Recent studies have demonstrated significant influences of posttranscriptional regulation by microRNA (miRNA) on HF development. The current study aims to investigate how miRNAs regulate Wnt/β-catenin to control HF inductivity of DP cells by performing microarray analysis in early- and late-passage DP cells and transfecting with miRNAs inhibitor or mimic. Results showed early-passage DP cells strongly expressed miRNAs related to inhibition of noncanonical Wnt pathways. In late-passage DP cells, miRNAs capable of inhibiting the canonical Wnt/β-catenin pathway were upregulated, in addition to the miRNAs targeting the noncanonical Wnt pathway. Moreover, we verified that β-catenin expression was downregulated by miR-195-5p overexpression in dose manner. Meanwhile LRP6 expression was downregulated in both protein and mRNA as well as the genes involved in the hair inductivity of DP cells. These results suggest that the appearance of miRNAs that suppress the Wnt/β-catenin pathway may be responsible for the loss of ability of DP cells in culture and miR-195-5p is the potential key factor involved in regulating HF inductivity of DP cells.
| S-EPMC5937601 | biostudies-literature
Project description:The dermal papilla (DP) of the hair follicle plays crucial roles in the hair follcie morphogenesis and cycling. Thus, the elucication of human DP molecular signature is of great interest. DP cell culture by conventional method impairs intrinsic properties of DP cells. Isolatoion of human DP is hampered by the lack of specific cell surface markers. Thus, it still depends on manual microdissection, with which the removal of minor contamination is unfeasible. Cultured DP cells are mostly pure. Aggregation of cultured DP cells was shown to restore some intrinsic properties in cultured DP cells. Fibroblasts are distinct dermal cell population and provide baseline for DP arrays.
2011-08-11 | GSE31324 | GEO
Project description:The dermal papilla (DP) of the hair follicle plays crucial roles in the hair follcie morphogenesis and cycling. Thus, the elucication of human DP molecular signature is of great interest. DP cell culture by conventional method impairs intrinsic properties of DP cells. Isolatoion of human DP is hampered by the lack of specific cell surface markers. Thus, it still depends on manual microdissection, with which the removal of minor contamination is unfeasible. Cultured DP cells are mostly pure. Aggregation of cultured DP cells was shown to restore some intrinsic properties in cultured DP cells. Fibroblasts are distinct dermal cell population and provide baseline for DP arrays. Four sets of Genechip microarrays were generated from freshly-microdissected DPs (fDP), cultured DP cells (cDP), cultured fibroblasts (Fibro) collected from respective volunteers. Two sets of Genechips were additionally prepared from aggregated DP cells (agDP) and cultured DP cells which were used for the generation of agDPs (each set derived from respective volunteer). These Genechips can be compared to elucidate the genes possibly contribute to intrinsic property of intact human DPs. For instance, comparisons between cultured DP (cDP) and fibroblast (Fibro) or between aggregated DP (agDP) and cDP could sort out potential DP signature genes, as each population is predominantly consisted of DP cells. When the expression levels of those genes were compared between fDP and cDP chips, the genes up- or equally expressed in fDPs should represent DP signature genes.
2011-08-10 | E-GEOD-31324 | biostudies-arrayexpress
Project description:Much is still unknown about the molecular regulatory networks which govern the dermal papilla’s (DP) ability to induce hair follicle regeneration, a capacity which gradually decreases with age. DP and dermal sheath cup (DSC) cells from mature, anagen phase, hair follicles were manually microdissected from fresh frozen sections of 16-18 week human fetal scalp and 30-60 year old adult male scalp. Interfollicular dermal (IFD) fibroblasts were harvested for comparison. RNA-seq libraries from each cell population were prepared with Nugen’s Ovation RNA-Seq and Ultralow Library systems, sequenced to approximately 100 million total reads. A set of 121 genes was identified as significantly upregulated in fetal DP cells, as compared to both fetal DSC and IFD populations. Wnt/β-catenin, Shh, FGF, BMP, and Notch signaling pathways were significantly enriched among those genes differentially expressed between fetal and adult DP cells. Among them, Spondin-1, a Wnt agonist, was chosen for verification and can rescue hair follicle regeneration in skin reconstitution assays using cells from adult mice. Additionally, twenty-nine transcription factors were significantly upregulated in fetal DP compared to adult DP cells. Of those, seven transcription factor binding motifs were significantly enriched in the candidate promoter regions of differentially expressed genes between fetal and adult DP cells, suggesting a combinatorial regulatory role in the fetal DP phenotype. Further investigation into these regulators is warranted to determine if these proteins and/or associated pathways plays a role in the maintenance or modulation of DP cells to induce hair regeneration.
2020-11-16 | GSE149189 | GEO
Project description:During the epidemic of the dengue virus (DENV) infection in Taiwan in 2014 and 2015, we observed an abnormally high frequency of increased scalp hair shedding in infected individuals that could not be explained by telogen effluvium. In this study, the mechanism of hair loss caused by DENV was explored. Human hair follicle dermal papilla cells (HFDPCs) are essential for hair follicle morphogenesis and cycling. Thus, we established an in vitro DENV infection model in HFDPCs. On immunofluorescence analysis, HFDPCs that were susceptible to DENV infection responded to type I interferon (IFN) treatment, and the cells showed antibody-dependent enhancement (ADE) effect. The expression of the pro-inflammatory cytokines, interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α), revealed an inflammatory response in DENV-infected HFDPCs. In particular, DENV infection impaired cell viability, and it activated caspase-associated cell death signaling in HFDPCs. In conclusion, our data indicate that direct infection with DENV causes inflammation and cell death in HFDPCs, which is involved in the mechanisms of hair loss after DENV infection. The knowledge of DENV infection in an immune-privileged tissue, such as hair follicles, may suggest their use for further studies on post-dengue fatigue syndrome (PDFS).
| S-EPMC6110916 | biostudies-literature
Project description: Not available
| S-EPMC3947143 | biostudies-literature
Project description:Dengue virus (DENV)-mediated hair loss is one of the post-dengue fatigue syndromes and its pathophysiology remains unknown. Whether long-term or persistent infection with DENV in the scalp results in hair loss is unclear. In this study, we cultured human dermal fibroblasts (WS1 cells) and primary human hair-follicle dermal papilla cells (HFDPCs) in the long term with DENV-2 infection. The production of virion, the expression of inflammatory and anti-virus genes, and their signaling transduction activity in the infected cells were analyzed. DENV-2 NS3 protein and DENV-2 5' UTR RNA were detected in fibroblasts and HFDPCs that were subjected to long-term infection with DENV-2 for 33 days. A significant amount of DENV-2 virion was produced by both WS1 cells and HFDPCs in the first two days of acute infection. The virion was also detected in WS1 cells that were infected in the long term, but HFDPCs failed to produce DENV-2 after long-term culture. Type I and type III interferons, and inflammatory cytokines were highly expressed in the acute phase of DENV infection in HFPDC and WS1 cells. However, in the long-term cultured cells, modest levels of anti-viral protein genes were expressed and we observed reduced signaling activity, which was correlated with the level of virus production changes. Long-term infection of DENV-2 downregulated the expression of hair growth regulatory factors, such as Rip1, Wnt1, and Wnt4. This in vitro study shows that the long-term infection with DENV-2 in dermal fibroblasts and dermal papilla cells may be involved with the prolonged-DENV-infection-mediated hair loss of post-dengue fatigue syndrome. However, direct evidence for viral replication in the human hair of a dengue victim or animal infection model is required.
| S-EPMC7150742 | biostudies-literature
Project description:The dermal papilla comprises the specialised mesenchymal cells at the base of the hair follicle. Communication between dermal papilla cells and the overlying epithelium is essential for differentiation of the hair follicle lineages. We report that Sox2 is expressed in all dermal papillae at E16.5, but from E18.5 onwards expression is confined to a subset of dermal papillae. In postnatal skin, Sox2 is only expressed in the dermal papillae of guard/awl/auchene follicles, whereas CD133 is expressed both in guard/awl/auchene and in zigzag dermal papillae. Using transgenic mice that express GFP under the control of the Sox2 promoter, we isolated Sox2(+) (GFP(+)) CD133(+) cells and compared them with Sox2(-) (GFP(-)) CD133(+) dermal papilla cells. In addition to the 'core' dermal papilla gene signature, each subpopulation expressed distinct sets of genes. GFP(+) CD133(+) cells had upregulated Wnt, FGF and BMP pathways and expressed neural crest markers. In GFP(-) CD133(+) cells, the hedgehog, IGF, Notch and integrin pathways were prominent. In skin reconstitution assays, hair follicles failed to form when dermis was depleted of both GFP(+) CD133(+) and GFP(-) CD133(+) cells. In the absence of GFP(+) CD133(+) cells, awl/auchene hairs failed to form and only zigzag hairs were found. We have thus demonstrated a previously unrecognised heterogeneity in dermal papilla cells and shown that Sox2-positive cells specify particular hair follicle types.
| S-EPMC2730408 | biostudies-literature
Project description:Systematic ablation of previously identified dermal papilla (DP) signature genes in embryonic DP precursors will reveal their functional roles during hair follicle morphogenesis. In this study, we validate Enpp2/Autotaxin as one of the highest expressed signature genes in postnatal DP, and demonstrate specific expression of this lysophosphatidic acid (LPA)-generating enzyme in embryonic dermal condensates. We further identify dermal and epidermal expression of several LPA receptors, suggesting that LPA signaling could contribute to follicle morphogenesis in both mesenchymal and epithelial compartments. We then use the recently characterized Cre-expressing Tbx18 knock-in line to conditionally ablate Enpp2 in embryonic DP precursors. Despite efficient gene knockout in embryonic day 14.5 (E14.5) dermal condensates, morphogenesis proceeds regularly with normal numbers, lengths, and sizes of all hair follicle types, suggesting that Enpp2 is not required for hair follicle formation. To interrogate DP signature gene expression, we finally isolate control and Enpp2-null DP precursors and identify the expression and upregulation of LIPH, an alternative LPA-producing enzyme, suggesting that this gene could functionally compensate for the absence of Enpp2. We conclude that future coablation of both LPA-producing enzymes or of several LPA receptors may reveal the functional role of LPA signaling during hair follicle morphogenesis.
| S-EPMC3748178 | biostudies-literature
Project description:Hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) are crucial in the biogenesis and maintenance of hair follicles (HFs). This study demonstrated that a fragment derived from aminoacyl-tRNA synthetase-interacting multifunctional protein1 (AIMP1) secreted from HFSCs activated DPCs and maintained HF homeostasis. A histological analysis revealed that AIMP1 levels in HF decreased with hair loss. Hair regrowth in AIMP1-induced mice was faster than in non-induced mice. Deletion mapping revealed 41 amino acids (TN41, aa 6-46) as the active region of AIMP1. The N-terminal peptide fragment of AIMP1 generated by MMP1 was secreted from Wnt-treated HFSCs to activate DPCs. TN41 activated Akt and ERK, increased β-catenin, and enhanced DPC activation. TN41 promoted hair shaft elongation in cultured human HFs and improved the hair-inducing activity of cultured DPC spheroids. Our findings suggest that the AIMP1 fragment secreted from HFSCs stimulates active hair regrowth through activating DPCs.
| S-EPMC11528461 | biostudies-literature