The Role of the Microenvironment on the Localization of Hair and Skin Nonuniform Pigmented Spots in Mice with a Targeted Mutation in the Endothelin B Receptor
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1292725 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In mammals, severe mutations in genes encoding factors critical for developing melanocytes often lead to a total loss of melanin-dependent skin and hair pigmentation. However, even null mutations in the gene encoding the G protein-coupled Endothelin-3 receptor EDNRB are associated with locally restricted pigmented spots at the head and tail on an otherwise totally white coat. Here, we investigate the developmental mechanism of these nonuniform pigmented spots in Ednrb-deficient mice and show that the local microenvironment, particularly the presence of enriched KIT ligand (KITL), dictates the appearance of these spots during development. Using a variety of transcriptomic profiling analyses and genetic and biochemical manipulations both in vivo and in vitro, we show that in E11.5 Ednrb-deficient embryos, a high expression level of KITL surrounds melanoblasts in the caudal region but not in the trunk region. The genetic reduction of KITL/KIT signaling in Ednrb-deficient miceleads to a complete loss of these nonuniform pigmented spots in the head and caudal regions. Moreover, the intradermal injection of anti-KIT antibody in the head region of adult Ednrb-deficient mice significantly reduces hair pigmentation in the secondary hair cycle. Furthermore, the exogenous addition of KITL rescues Ednrb-deficient melanoblasts from the neural crest cells in the trunk region, likely by stimulating MITF expression. Hence, these findings underscore the significance of the microenvironment for the appearance and localization of pigment spots and highlight the role of KITL as a major determinant of this microenvironment.
2025-07-22 | GSE302869 | GEO
Project description:Proteomic genotyping is the use of genetically variant peptides (GVPs), detected in a forensic protein sample, to infer the genotype of corresponding non-synonymous SNP alleles in the donor’s genome. This process does not depend on the presence of accessible or useable DNA in a sample. This makes proteomic genotyping an attractive alternative for analysis of problematic forensic samples, such as hair shafts, degraded bones or teeth, fingermarks, or sexual assault evidence. To demonstrate the concept in hair shafts, we developed an optimized sample processing protocol that could be used with high effectiveness on single hairs. This allows us to determine if the detected profiles of genetically variant peptides are robust and result in a consistent profile of inferred SNP alleles regardless of the chemical or biological history of the sample. Several real world scenarios have been evaluated. Here we include a study of four European subjects that had both pigmented and non-pigmented (or gray and non-gray) hair shafts. We tested whether (a) protein profiles change as a result of the loss of pigmentation and (b) these changes were reflected in the inferred genotype derived from detection of genetically variant peptides. Using this information, we can determine whether the resulting GVP profiles are more dependent on the biological context of pigmentation status or the underlying genotype.
2020-05-27 | PXD016156 | Pride
Project description:The hair follicle bulb is the only site of pigment production for the hair shaft and melanogenically active melanocytes are located in the upper hair matrix. We conducted a microarray study to discover gene expression patterns that may be implicated in the lack of melanogenesis in gray hair follicles (HF). Pigmented and non-pigmented HFs collected from the same individuals were micro-dissected into the lower one third including the hair bulb (HB) and the upper hair shaft and sheaths (HS) including the bulge region. Microarray data was verified with qPCR and immunohistochemistry. Target effects were evaluated in vitro on human epidermal melanocytes (HEMs). In comparison to pigmented HS and HBs, several nucleotide excision repair (NER) family genes exhibited statistically significant lower expression both in non-pigmented HS and non-pigmented HB. These genes were identified as ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, XPA, NTPBP, HCNP, DDB2 and POLH. Immunohistochemistry showed consistent results. By siRNA interference we also detected that a deficiency in ERCC3 in melanocytes reduced the ability to produce melanin in vitro. Our results suggest that loss of NER gene function may lead to DNA damage and mutation accumulation in melanocytes, which may possibly lead to cell death. Further, a loss of ERCC3 function may lead to reduced gene transcription and this in turn may lead to reduced melanin production ability. These results offer a new insight into the molecular changes that occur in non-pigmented HF and may also provide novel information with regard to melanogenesis and its regulation.
2010-10-18 | GSE24009 | GEO
Project description:Progenitor cell death and dermal papilla relocation during the regression phase of the hair growth cycle are essential for stem cell activation and follicle regeneration. This drastic follicle remodeling is coordinated by dermal sheath (DS) smooth muscle contraction, but how DS-generated forces are regulated is unknown. Here, we identify endothelin signaling - a potent vasoconstriction-regulating pathway - as the key activating mechanism of DS contraction. Pharmacological blocking or genetic ablation of both endothelin receptors, ETA and ETB, impedes DS contraction and halts follicle regression. Progenitors at the epithelial strand bottleneck are the main source of endothelin ligand ET-1, which is required for follicle regression. ET signaling in DS cells and downstream contraction is dynamically regulated by cytoplasmic Ca2+ levels via cell membrane and sarcoplasmic reticulum calcium channels. Together, these findings illuminate an epithelial-mesenchymal-interaction paradigm in which progenitors - before undergoing programmed cell death - control the contraction of the surrounding sheath smooth muscle to orchestrate homeostatic tissue regression and follicle reorganization.
2022-10-31 | GSE215133 | GEO
Project description:Progenitor-derived endothelin controls dermal sheath contraction for hair follicle regression
| PRJNA888980 | ENA
Project description:Transcriptional analysis of pigmented and non-pigmented potato tuber flesh using POCI 44k microarrays
2010-01-01 | E-TABM-787 | biostudies-arrayexpress
Project description:Transcriptional analysis of pigmented and non-pigmented potato tuber flesh using POCI 44k microarrays
2010-01-01 | E-TABM-788 | biostudies-arrayexpress
Project description:Time resolved phosphorylation changes were measured the melanoma cell lines A2058 and UACC257. An endothelin B receptor knockout of UACC257 was processed in parallel. Protein abundance was also compared at the latest time point of the study (90 min) using DIA-SWATH
2019-10-09 | PXD012316 | Pride
Project description:Endothelin signaling is one of the essential signaling pathways that control vertebrate development. Dysregulated Endothelin signaling plays an important role in the pathogenesis of human diseases such as Hirschsprung’s disease, pulmonary hypertension and cancer. However, the downstream transcriptional program and transcriptional factors of Endothelin signaling have been incompletely understood. Here, we used RNA-sequencing to identify the genes regulated by Endothelin signaling in the neural crest, where Endothelin signaling functions primarily during development. We further demonstrate that Endothelin induces gene expression through the de-repression of the MADS Box transcription factor MEF2C. Moreover, in the Mef2c gene locus, we identified an Endothelin responsive cis-regulatory element which functions as a central component of an Endothelin-MEF2C positive feedback transcriptional mechanism that regulates downstream gene expression.
2016-11-15 | GSE47919 | GEO
Project description:Information about protein expression in rice grain across both pigmented and non-pigmented rice varieties is still relatively scarce. The data provided here represent proteomic data obtained from selected 6 Malaysian local rice varieties with varying pigmentations (black, red and white). The selected pigmented rice varieties such as black (BALI and Pulut hitam 9) and red rice (MRQ100 and MRM16) have shown high antioxidant activities and non-pigmented rice (MRQ76 and MR297) contain amino acid and micronutrient contents. This project aimed to obtain global protein expression profile as well as differential protein expression between the selected pigmented and non-pigmented rice varieties particularly proteins with their functions responsible for nutritional (i.e. antioxidant, folate and low glycaemic index) and quality (i.e. aromatic) traits. Integration of this proteomics dataset with other available in-house omics data could facilitate the identification of significant functional markers related to nutritional and quality traits. Total proteins were prepared from dehusked matured seeds harvested from three different rice plants of each variety (3 protein samples per variety). The proteins were trypsin digested before subjected to SWATH-MS proteomics analysis. Proteins were identified by matching tandem mass (MS/MS) spectra from both 1D and 2D IDA to Oryza sativa japonica and indica rice databases available at UniProt by using ProteinPilot software (v4.2) (AB Sciex). Quantification of proteins was carried out by determining protein peak areas extracted from SWATH analysis data sets using PeakView (v2.1) (AB Sciex) software. Differentially expressed protein between varieties were identified using T-test analysis with a set threshold for fold change ± 1.5 and p‐value < 0.05.
2020-04-27 | PXD018338 | Pride