Vertebrates exhibit patterned epidermis, exemplified by scales/interscales in mice tails and grooves/ridges on the human skin surface (microtopography). Although the role of spatiotemporal regulation of stem cells (SCs) has been implicated in this process, the mechanism underlying the development of such epidermal patterns is poorly understood. Here, we show that collagen XVII (COL17), a niche for epidermal SCs, helps stabilize epidermal patterns. Gene knockout and rescue experiments revealed that COL17 maintains the width of the murine tail scale epidermis independently of epidermal cell polarity. Skin regeneration after wounding was associated with slender scale epidermis, which was alleviated by overexpression of human COL17. COL17-negative skin in human junctional epidermolysis bullosa showed a distinct epidermal pattern from COL17-positive skin that resulted from revertant mosaicism. These results demonstrate that COL17 contributes to defining mouse tail scale shapes and human skin microtopography. Our study sheds light on the role of the SC niche in tissue pattern formation.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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We thank Ms. Megumi Takehara for their technical assistance. We also thank Professor Kim B. Yancey for providing K14-hCOL17 transgenic mice.
Y.W. performed the experiments, analyzed the data, interpreted the results, and wrote the manuscript. H.Kitahata analyzed the data, interpreted the results, and wrote the manuscript. H.Kosumi, M.W., Y.F., S.T., S.I.O., T.H., and W.N. performed the experiments and analyzed the data. M.N. and H.S. interpreted the results and supervised the study. K.N. designed the experiments, analyzed the data, interpreted the results, wrote the manuscript and supervised the study.
This work was funded by AMED to K.N. (20ek0109380h0003), the Lydia O’Leary Memorial Pias Dermatological Foundation to W.N., JST CREST (JPMJCR15D2) to M.N., and Five-star Alliance in NJRC Master. & Dev to H.Kitahata/M.N.
The authors declare no competing interests.
Ethics Approval and consent to participate
The institutional review board of the Hokkaido University Graduate School of Medicine approved all human studies described above (ID: 13-043). The study was conducted according to the principles of the Declaration of Helsinki. The participant provided written informed consent.
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Wang, Y., Kitahata, H., Kosumi, H. et al. Collagen XVII deficiency alters epidermal patterning. Lab Invest 102, 581–588 (2022). https://doi.org/10.1038/s41374-022-00738-2