Similar Datasets
Project description:TD keratinocytes in the adult skin possess molecular characteristics of other epidermal lineages, thereby giving it the unique tri-potential capacity
2024-01-29 | GSE228988 | GEO
Project description:TD keratinocytes in the adult skin possess molecular characteristics of other epidermal lineages, thereby giving it the unique tri-potential capacity
2024-01-29 | GSE228987 | GEO
Project description:In mammalian skin, Merkel cells are mechanoreceptor cells that are required for the perception of gentle touch. Recent evidence indicates that mature Merkel cells descend from the proliferative layer of skin epidermis; however, the stem cell niche for Merkel cell homeostasis has not been reported. Here, we provide genetic evidence for maintenance of mature Merkel cells during homeostasis by Krt17+ stem cells located in epidermal touch domes of hairy skin and in the tips of the rete ridges of glabrous skin. Lineage tracing analysis indicated that the entire pool of mature Merkel cells is turned over every 7-8 weeks in the adult epidermis and that Krt17+ stem cells also maintain squamous differentiation in the touch dome and in glabrous skin. Finally, selective genetic ablation of Krt17+ touch-dome keratinocytes indicates that these cells, and not mature Merkel cells, are primarily responsible for maintaining innervation of the Merkel cell-neurite complex.
| S-EPMC3700648 | biostudies-literature
Project description:The touch dome is a highly patterned mechanosensory structure in the epidermis composed of specialized keratinocytes in juxtaposition with innervated Merkel cells. The touch dome epithelium is maintained by tissue-specific stem cells, but the signals that regulate the touch dome are not known. We identify touch dome stem cells that are unique among epidermal cells in their activated Hedgehog signaling and ability to maintain the touch dome as a distinct lineage compartment. Skin denervation reveals that renewal of touch dome stem cells requires a perineural microenvironment, and deleting Sonic hedgehog (Shh) in neurons or Smoothened in the epidermis demonstrates that Shh is an essential niche factor that maintains touch dome stem cells. Up-regulation of Hedgehog signaling results in neoplastic expansion of touch dome keratinocytes but no Merkel cell neoplasia. These findings demonstrate that nerve-derived Shh is a critical regulator of lineage-specific stem cells that maintain specialized sensory compartments in the epidermis.
| S-EPMC4466733 | biostudies-literature
Project description:A new langerin(+) DC subset has recently been identified in murine dermis (langerin(+) dDC), but the lineage and functional relationships between these cells and langerin(+) epidermal Langerhans cells (LC) are incompletely characterized. Selective expression of the cell adhesion molecule EpCAM by LC allowed viable LC to be easily distinguished from langerin(+) dDC in skin and lymphoid tissue and ex vivo as well. Differential expression of EpCAM and langerin revealed the presence of at least 3 distinct skin DC subsets. We determined that LC and langerin(+) dDC exhibit different migratory capabilities in vitro and repopulate distinct anatomic compartments in skin at different rates after conditional depletion in vivo. Langerin(+) dDC, in contrast to LC, did not require TGFbeta1 for development. Carefully timed gene gun immunization studies designed to take advantage of the distinct repopulation kinetics of langerin(+) dDC and LC revealed that langerin(+) dDC were required for optimal production of beta-galactosidase-specific IgG2a/c and IgG2b in the acute phase. In contrast, immunization via LC-deficient skin resulted in persistent and strikingly reduced IgG1 and enhanced IgG2a Ab production. Our data support the concepts that LC and langerin(+) dDC represent distinct DC subsets that have specialized functions and that LC are important immunoregulatory cells. The presence of at least 3 functionally distinct skin DC subsets may have particular relevance for vaccines that are administered epicutaneously.
| S-EPMC2651335 | biostudies-literature
Project description:Human embryonic stem (hES) cells are an attractive source of cellular material for scientific, diagnostic, and potential therapeutic applications. Protocols are now available to direct hES cell differentiation to specific lineages at high purity under relatively defined conditions; however, researchers must establish the functional similarity of hES cell derivatives and associated primary cell types to validate their utility. Using retinoic acid to initiate differentiation, we generated high-purity populations of keratin 14+ (K14) hES cell-derived keratinocyte (hEK) progenitors and performed microarray analysis to compare the global transcriptional program of hEKs and primary foreskin keratinocytes. Transcriptional patterns were largely similar, though gene ontology analysis identified that genes associated with signal transduction and extracellular matrix were upregulated in hEKs. In addition, we evaluated the ability of hEKs to detect and respond to environmental stimuli such as Ca(2+), serum, and culture at the air-liquid interface. When cultivated on dermal constructs formed with collagen gels and human dermal fibroblasts, hEKs survived and proliferated for 3 weeks in engineered tissue constructs. Maintenance at the air-liquid interface induced stratification of surface epithelium, and immunohistochemistry results indicated that markers of differentiation (e.g., keratin 10, involucrin, and filaggrin) were localized to suprabasal layers. Although the overall tissue morphology was significantly different compared with human skin samples, organotypic cultures generated with hEKs and primary foreskin keratinocytes were quite similar, suggesting these cell types respond to this microenvironment in a similar manner. These results represent an important step in characterizing the functional similarity of hEKs to primary epithelia.
| S-EPMC2810995 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-01-08 | E-GEOD-76674 | biostudies-arrayexpress
Project description:The first point of our body's contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments. Specific deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and primary afferent mechanical sensitivity, thus positioning keratinocyte-released ATP to sensory neuron P2X4 signaling as a critical component of baseline mammalian tactile sensation. These experiments lay a vital foundation for subsequent studies into the dysfunctional signaling that occurs in cutaneous pain and itch disorders, and ultimately, the development of novel topical therapeutics for these conditions.
| S-EPMC5777822 | biostudies-literature
Project description:BackgroundOne challenge of systems biology is the integration of new data into the preexisting, and then re-interpretation of the integrated data. Here we use readily available metaanalysis computational methods to integrate new data on the transcriptomic effects of EGF in primary human epidermal keratinocytes with preexisting transcriptomics data in keratinocytes and in EGF-treated non-epidermal cell types.ResultsWe find that EGF promotes keratinocyte proliferation, attachment and motility and, surprisingly, induces DUSPs that attenuate the EGF signal. Our metaanalysis identified overlapping effects of EGF with those of IL-1 and IFNγ, activators of keratinocyte in inflammation and wound healing. We also identified the genes and pathways suppressed by EGF but induced by agents promoting epidermal differentiation. Metaanalysis comparison with the EGF effects in other cell types identified extensive similarities between responses in keratinocytes and in other epithelial cell types, but specific differences with the EGF effects in endothelial cells, and in transformed, oncogenic epithelial cell lines.ConclusionsThis work defines the specific transcriptional effects of EGF on human epidermal keratinocytes. Our approach can serve as a suitable paradigm for integration of new omics data into preexisting databases and re-analysis of the integrated data sets.
| S-EPMC3608085 | biostudies-literature
Project description:The Sonic hedgehog (Shh) signaling pathway regulates developmental, homeostatic, and repair processes throughout the body. In the skin, touch domes develop in tandem with primary hair follicles and contain sensory Merkel cells. The developmental signaling requirements for touch dome specification are largely unknown. We found dermal Wnt signaling and subsequent epidermal Eda/Edar signaling promoted Merkel cell morphogenesis by inducing Shh expression in early follicles. Lineage-specific gene deletions revealed intraepithelial Shh signaling was necessary for Merkel cell specification. Additionally, a Shh signaling agonist was sufficient to rescue Merkel cell differentiation in Edar-deficient skin. Moreover, Merkel cells formed in Fgf20 mutant skin where primary hair formation was defective but Shh production was preserved. Although developmentally associated with hair follicles, fate mapping demonstrated Merkel cells primarily originated outside the hair follicle lineage. These findings suggest that touch dome development requires Wnt-dependent mesenchymal signals to establish reciprocal signaling within the developing ectoderm, including Eda signaling to primary hair placodes and ultimately Shh signaling from primary follicles to extrafollicular Merkel cell progenitors. Shh signaling often demonstrates pleiotropic effects within a structure over time. In postnatal skin, Shh is known to regulate the self-renewal, but not the differentiation, of touch dome stem cells. Our findings relate the varied effects of Shh in the touch dome to the ligand source, with locally produced Shh acting as a morphogen essential for lineage specification during development and neural Shh regulating postnatal touch dome stem cell maintenance.
| S-EPMC4944988 | biostudies-literature