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Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [ATAC-seq]

ABSTRACT: TD keratinocytes in the adult skin possess molecular characteristics of other epidermal lineages, thereby giving it the unique tri-potential capacity

ORGANISM(S): Mus musculus

PROVIDER: GSE228987 | GEO | 2024/01/29

REPOSITORIES: GEO

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Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [RNA-seq]

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

Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages.

Project description:The touch dome (TD) keratinocytes are specialized epidermal cells that intimately associate with the light touch sensing Merkel cells (MCs). The TD keratinocytes function as a niche for the MCs and can induce de novo hair follicles upon stimulation; however, how the TD keratinocytes are maintained during homeostasis remains unclear. scRNA-seq identified a specific TD keratinocyte marker, Tenascin-C (TNC). Lineage tracing of Tnc-expressing TD keratinocytes revealed that these cells maintain themselves as an autonomous epidermal compartment and give rise to MCs upon injury. Molecular characterization uncovered that, while the transcriptional and chromatin landscape of the TD keratinocytes is remarkably similar to that of the interfollicular epidermal keratinocytes, it also shares certain molecular signatures with the hair follicle keratinocytes. Our study highlights that the TD keratinocytes in the adult skin have molecular characteristics of keratinocytes of diverse epidermal lineages.

| S-EPMC10798558 | biostudies-literature

Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages.

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

2024-01-29 | GSE228989 | GEO

Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages.

Project description:Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages.

| PRJNA952502 | ENA

Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [RNA-seq]

Project description:Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [RNA-seq]

| PRJNA952506 | ENA

Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [ATAC-seq]

Project description:Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [ATAC-seq]

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The touch dome defines an epidermal niche specialized for mechanosensory signaling.

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.

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Neural Hedgehog signaling maintains stem cell renewal in the sensory touch dome epithelium.

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.

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Co-option of epidermal cells enables touch sensing.

Project description:The epidermis is equipped with specialized mechanosensory organs that enable the detection of tactile stimuli. Here, by examining the differentiation of the tactile bristles, mechanosensory organs decorating the Drosophila adult epidermis, we show that neighbouring epidermal cells are essential for touch perception. Each mechanosensory bristle signals to the surrounding epidermis to co-opt a single epidermal cell, which we named the F-Cell. Once specified, the F-Cell adopts a specialized morphology to ensheath each bristle. Functional assays reveal that adult mechanosensory bristles require association with the epidermal F-Cell for touch sensing. Our findings underscore the importance of resident epidermal cells in the assembly of functional touch-sensitive organs.

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A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development.

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.

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