Comparative Spatial Transcriptomic and Single-Cell Analyses of Human Nail Units and Hair Follicles Show Transcriptional Similarities between the Onychodermis and Follicular Dermal Papilla.

The nail unit and hair follicle are both hard keratin-producing organs that share various biological features. In this study, we used digital spatial profiling and single-cell RNA sequencing to define a spatially resolved expression profile of the human nail unit and hair follicle. Our approach showed the presence of a nail-specific mesenchymal population called onychofibroblasts within the onychodermis. Onychodermis and follicular dermal papilla both expressed Wnt and bone morphogenetic protein signaling molecules. In addition, nail matrix epithelium and hair matrix showed very similar expressions profile, including the expression of hard keratins and HOXC13, a transcriptional regulator of the hair shaft. Integration of single-cell RNA sequencing and digital spatial profiling data through computational deconvolution methods estimated epithelial and mesenchymal cell abundance in the nail- and hair-specific regions of interest and revealed close transcriptional similarity between these major skin appendages. To analyze the function of bone morphogenetic proteins in nail differentiation, we treated cultured human nail matrix keratinocytes with BMP5, which are highly expressed by onychofibroblasts. We observed increased expressions of hard keratin and its regulator genes such as HOXC13. Collectively, our data suggest that onychodermis is the counterpart of dermal papilla and that BMP5 in onychofibroblasts plays a key role in the differentiation of nail matrix keratinocytes.

Characterization of the Onychomatricodermis Containing Onychofibroblasts of the Nail Unit : Histology, Immunohistochemistry, and Electron Microscopic Study.

BACKGROUND: We recently discovered the presence of specialized nail mesenchyme below the nail matrix and designated it as onychomatricodermis. OBJECTIVE: We did further research to characterize the histologic, histochemical, immunohistochemical and ultrastructural features of the onychomatricodermis containing onychofibroblasts in the nail unit. METHODS: Ten polydactyly nail unit specimens and 8 nail matrix biopsies were included. H&E-stained slides were reviewed. We did Alcian blue staining and Masson Trichrome staining, as well as immunohistochemical staining for type I collagen, CD10, CD13 and CD34. In addition, polydactyly nail units were examined by transmission electron microscopy. RESULTS: In H&E staining, the specialized mesenchyme called onychomatricodermis was observed to be slightly distant from the undersurface of the nail matrix and be less eosinophilic area. Onychomatricodermal onychofibroblasts showed light purple abundant cytoplasm. Masson Trichrome staining revealed fewer collagen fibers within the onychomatricodermis. In Alcian blue staining the onychomatricodermis showed mucin deposition within the onychofibroblasts and around them. Immunohistochemically, type I collagen was expressed much less in the onychomatricodermis while it was strongly expressed elsewhere in the nail unit. In nail matrix biopsy specimens onychomatricodermal onychofibroblasts expressed CD10 and CD13 strongly, and expressed CD34 as well. Ultrastructurally, collagen fibrils were found sparsely within the onychomatricodermis, whereas collagen fibrils were densely distributed in the dermis of other parts of the nail unit. CONCLUSION: We demonstrated that there was less collagen expression in the onychomatricodermis containing onychofibroblasts. In addition, we found morphological and immunohistochemical features of onychomatricodermal onychofibroblasts (onychofibroblasts of Dongyoun). These findings support the presence of onychomatricodermis containing onychofibroblasts in the nail unit.

Clinical characteristics and pathological depths of syringomas in 94 Korean patients.

BACKGROUND: Syringoma is a common benign tumor with eccrine origin that typically occurs on the face of middle-aged women. Laser ablation with CO2 laser or Er:YAG laser has been widely used in the clinical field, often leading to scars due to its deep location. This study aimed to investigate clinical characteristics and pathological depths of the lesions in syringoma patients. MATERIALS AND METHODS: Syringoma patients, pathologically confirmed at Samsung medical center (Seoul, Korea) from January 1996 to March 2019, were analyzed. Clinical characteristics such as the location of lesion, age, and sex, and pathological depths of the lesions were investigated, and univariable and multivariable analyses were done for these factors. RESULTS: Of total 94 syringomas, 17.0% were located on periocular area, 10.6% on forehead, 34.0% on head and neck areas excluding periocular area and forehead, and 38.3% on trunk and extremities. The mean depth of syringoma from the surface including stratum corneum to the deepest stromal location was 1174.14 ± 1142.95 µm for periocular area, 1055.93 ± 247.76 µm for forehead, 1488.06 ± 1217.36 µm for other areas of head and neck including scalp, and 1169.53 ± 349.2 for the lesions located at trunk and extremities including external genitalia. No significant correlation was observed from univariable analysis and multivariable analysis by age, sex, and site of lesion. CONCLUSION: Our findings offer valuable information of the mean depth of syringoma at different sites, which can be taken into consideration for successful treatment without adverse events such as scarring.

The concept of nail matrix onychodermis (onychomatricodermis) in the nail unit: Histology and elastin immunohistochemistry.

BACKGROUNDS: We previously demonstrated the presence of onychodermis below nail matrix and nail bed. Because nail matrix is a producer of nail plate, we hypothesized that onychodermis below nail matrix could be the nail counterpart of follicular dermal papilla. In this study, we sought to further characterize histologic, histochemical, and immunohistochemical features of nail matrix onychodermis. METHODS AND RESULTS: Hematoxylin and eosin slides of 10 polydactyly nail units and 10 nail matrix biopsies from children and adults were reviewed. In polydactyly nail units, the onychodermis beneath nail matrix was characterized by onychofibroblasts showing abundant cytoplasm, and this area was slightly separated from the undersurface of the nail matrix. Nail matrix biopsy specimens also showed similar histology in the nail matrix onychodermis. Alcian blue stain demonstrated mucin deposition in onychofibroblasts within the nail matrix onychodermis. Immunohistochemically, elastin was rarely expressed in the nail matrix onychodermis while it was strongly expressed in the dermis of other areas of polydactyly nail units. Elastin was not expressed in follicular dermal papilla of terminal hair follicles of the scalp. CONCLUSION: Our findings demonstrate the presence and localization of nail matrix onychodermis (onychomatricodermis). Our study also demonstrates similar elastin expression patterns in the onychomatricodermis and follicular dermal papilla.