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

  • Author Footnotes
    6 These authors contributed equally to this work.
    Joonho Shim
    Footnotes
    6 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Author Footnotes
    6 These authors contributed equally to this work.
    Jihye Park
    Footnotes
    6 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Gulimila Abudureyimu
    Affiliations
    Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Min-Hee Kim
    Affiliations
    Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Jong Sup Shim
    Affiliations
    Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Kee-Taek Jang
    Affiliations
    Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Eun Ji Kwon
    Affiliations
    Department of Dermatology, Columbia University Irving Medical Center, New York, New York, USA
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  • Hyung-Suk Jang
    Affiliations
    Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Eunhye Yeo
    Affiliations
    Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea
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  • Jong Hee Lee
    Affiliations
    Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea
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  • Dongyoun Lee
    Correspondence
    Correspondence: Dongyoun Lee, Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.
    Affiliations
    Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Author Footnotes
    6 These authors contributed equally to this work.
      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.

      Abbreviations:

      BMP (bone morphogenetic protein), DEG (differentially expressed gene), DP (dermal papilla), DSP (digital spatial profiling), HF (hair follicle), HM (hair matrix), KRT (keratin), NME (nail matrix epithelium), NMK (nail matrix keratinocyte), OD (onychodermis), RNA-ISH (in situ RNA hybridization), ROI (region of interest), scRNA-seq (single-cell RNA sequencing)
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