Minoru Yuriguchi1, Hitomi Aoki1, Nobuhiko Taguchi2, Takahiro Kunisada3. 1. Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 5011194, Japan. 2. Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 5011194, Japan; General Reearch & Development Institute, Hoyu Co., Ltd., 1-12, Roboku, Nagakute, Aichi 4801136, Japan. 3. Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 5011194, Japan. Electronic address: tkunisad@gifu-u.ac.jp.
Abstract
BACKGROUND: After severe wounding, hair follicles were known to be regenerated de novo along with the re-epithelialization. However, the regenerated hairs lack pigmentation. OBJECTIVE: We aimed to find out the condition to regenerate pigmented hairs after severe wounding. METHODS: De novo hair regeneration was observed during the re-epithelialization process after the full thickness excision of dorsal skin. Hair pigmentation mechanism was assessed by the modulation of Wnt and Kit signalings. RESULTS: Stable regeneration of pigmented hairs was demonstrated when a wound was created to the mice during the anagen stage of the hair cycle. A significant increase in the number of melanocyte stem cells in the postnatal 1st anagen interfollicular skin of 5-week-old mice was observed. An increase of Wnt7a of the keratinocytes was observed in the skin at this stage, which may direct melanocyte stem cells to produce pigmented hairs in the regenerating follicles. This was supported by the finding that transgenic mice expressing the melanocyte stimulatory factor Kitl in their skin promoted the regeneration of pigmented hairs irrespective of the stage of the hair cycle. CONCLUSION: Our results provide a new insight into the intimate regulation process between two follicular stem cell systems, keratinocyte stem cells and melanocyte stem cells, during de novo hair regeneration after wounding.
BACKGROUND: After severe wounding, hair follicles were known to be regenerated de novo along with the re-epithelialization. However, the regenerated hairs lack pigmentation. OBJECTIVE: We aimed to find out the condition to regenerate pigmented hairs after severe wounding. METHODS: De novo hair regeneration was observed during the re-epithelialization process after the full thickness excision of dorsal skin. Hair pigmentation mechanism was assessed by the modulation of Wnt and Kit signalings. RESULTS: Stable regeneration of pigmented hairs was demonstrated when a wound was created to the mice during the anagen stage of the hair cycle. A significant increase in the number of melanocyte stem cells in the postnatal 1st anagen interfollicular skin of 5-week-old mice was observed. An increase of Wnt7a of the keratinocytes was observed in the skin at this stage, which may direct melanocyte stem cells to produce pigmented hairs in the regenerating follicles. This was supported by the finding that transgenic mice expressing the melanocyte stimulatory factor Kitl in their skin promoted the regeneration of pigmented hairs irrespective of the stage of the hair cycle. CONCLUSION: Our results provide a new insight into the intimate regulation process between two follicular stem cell systems, keratinocyte stem cells and melanocyte stem cells, during de novo hair regeneration after wounding.