SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes
Abstract Niche for stem cells profoundly influences their maintenance and fate during tissue homeostasis and pathological disorders; however, the underlying mechanisms and tissue‐specific features remain poorly understood. Here, it is reported that fatty acid desaturation catabolized by stearoyl‐coe...
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Wiley
2023-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202201949 |
| _version_ | 1797688123012939776 |
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| author | Yueqing Xue Liangyu Lin Qing Li Keli Liu Mingyuan Hu Jiayin Ye Jianchang Cao Jingjie Zhai Fanjun Zheng Yu Wang Tao Zhang Liming Du Cheng Gao Guan Wang Xuefeng Wang Jun Qin Xinhua Liao Xiangyin Kong Lydia Sorokin Yufang Shi Ying Wang |
| author_facet | Yueqing Xue Liangyu Lin Qing Li Keli Liu Mingyuan Hu Jiayin Ye Jianchang Cao Jingjie Zhai Fanjun Zheng Yu Wang Tao Zhang Liming Du Cheng Gao Guan Wang Xuefeng Wang Jun Qin Xinhua Liao Xiangyin Kong Lydia Sorokin Yufang Shi Ying Wang |
| author_sort | Yueqing Xue |
| collection | DOAJ |
| description | Abstract Niche for stem cells profoundly influences their maintenance and fate during tissue homeostasis and pathological disorders; however, the underlying mechanisms and tissue‐specific features remain poorly understood. Here, it is reported that fatty acid desaturation catabolized by stearoyl‐coenzyme A desaturase 1 (SCD1) regulates hair follicle stem cells (HFSCs) and hair growth by maintaining the bulge, niche for HFSCs. Scd1 deletion in mice results in abnormal hair growth, an effect exerted directly on keratin K14+ keratinocytes rather than on HFSCs. Mechanistically, Scd1 deficiency impairs the level of integrin α6β4 complex and thus the assembly of hemidesmosomes (HDs). The disruption of HDs allows the aberrant activation of focal adhesion kinase and PI3K in K14+ keratinocytes and subsequently their differentiation and proliferation. The overgrowth of basal keratinocytes results in downward extension of the outer root sheath and interruption of bulge formation. Then, inhibition of PI3K signaling in Scd1−/− mice normalizes the bulge, HFSCs, and hair growth. Additionally, supplementation of oleic acid to Scd1−/− mice reestablishes HDs and the homeostasis of bulge niche, and restores hair growth. Thus, SCD1 is critical in regulating hair growth through stabilizing HDs in basal keratinocytes and thus sustaining bulge for HFSC residence and periodic activity. |
| first_indexed | 2024-03-12T01:27:43Z |
| format | Article |
| id | doaj.art-c703916c64644668b7d7263e2411cdc5 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T01:27:43Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-c703916c64644668b7d7263e2411cdc52023-09-12T14:40:47ZengWileyAdvanced Science2198-38442023-02-01104n/an/a10.1002/advs.202201949SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal KeratinocytesYueqing Xue0Liangyu Lin1Qing Li2Keli Liu3Mingyuan Hu4Jiayin Ye5Jianchang Cao6Jingjie Zhai7Fanjun Zheng8Yu Wang9Tao Zhang10Liming Du11Cheng Gao12Guan Wang13Xuefeng Wang14Jun Qin15Xinhua Liao16Xiangyin Kong17Lydia Sorokin18Yufang Shi19Ying Wang20CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaSchool of Life Sciences Shanghai University Shanghai 200444 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaInstitute of Physiological Chemistry and Pathobiochemistry Cells in Motion Interfaculty Centre (CIMIC) University of Münster D‐48149 Münster GermanyCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaAbstract Niche for stem cells profoundly influences their maintenance and fate during tissue homeostasis and pathological disorders; however, the underlying mechanisms and tissue‐specific features remain poorly understood. Here, it is reported that fatty acid desaturation catabolized by stearoyl‐coenzyme A desaturase 1 (SCD1) regulates hair follicle stem cells (HFSCs) and hair growth by maintaining the bulge, niche for HFSCs. Scd1 deletion in mice results in abnormal hair growth, an effect exerted directly on keratin K14+ keratinocytes rather than on HFSCs. Mechanistically, Scd1 deficiency impairs the level of integrin α6β4 complex and thus the assembly of hemidesmosomes (HDs). The disruption of HDs allows the aberrant activation of focal adhesion kinase and PI3K in K14+ keratinocytes and subsequently their differentiation and proliferation. The overgrowth of basal keratinocytes results in downward extension of the outer root sheath and interruption of bulge formation. Then, inhibition of PI3K signaling in Scd1−/− mice normalizes the bulge, HFSCs, and hair growth. Additionally, supplementation of oleic acid to Scd1−/− mice reestablishes HDs and the homeostasis of bulge niche, and restores hair growth. Thus, SCD1 is critical in regulating hair growth through stabilizing HDs in basal keratinocytes and thus sustaining bulge for HFSC residence and periodic activity.https://doi.org/10.1002/advs.202201949bulgehair follicle stem cellshemidesmosomeskeratinocytesstearoyl‐CoA desaturase 1 |
| spellingShingle | Yueqing Xue Liangyu Lin Qing Li Keli Liu Mingyuan Hu Jiayin Ye Jianchang Cao Jingjie Zhai Fanjun Zheng Yu Wang Tao Zhang Liming Du Cheng Gao Guan Wang Xuefeng Wang Jun Qin Xinhua Liao Xiangyin Kong Lydia Sorokin Yufang Shi Ying Wang SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes Advanced Science bulge hair follicle stem cells hemidesmosomes keratinocytes stearoyl‐CoA desaturase 1 |
| title | SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes |
| title_full | SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes |
| title_fullStr | SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes |
| title_full_unstemmed | SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes |
| title_short | SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes |
| title_sort | scd1 sustains homeostasis of bulge niche via maintaining hemidesmosomes in basal keratinocytes |
| topic | bulge hair follicle stem cells hemidesmosomes keratinocytes stearoyl‐CoA desaturase 1 |
| url | https://doi.org/10.1002/advs.202201949 |
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