Ying Wang's research group from the Institute of Nutrition and Health discovered a new mechanism by which fatty acid metabolism regulates the formation of hair follicle stem cell microenvironment

Stem cell niches play an important role
in maintaining the resting state of stem cells and regulating the activity and fate of stem cells.
Although many studies have revealed the tissue-specific characteristics of stem cell niches in different tissues and organs, the mechanism of their formation and the maintenance mechanism of equilibrium state are still poorly
understood.
In the hair follicle, the mobilization of HFSCs is periodic, and the stem cell niche, the bulge region, regulates the resting and activation of HFSCs by integrating a variety of signals, ensuring that they can maintain hair growth
throughout life.

SCD1 is a rate-limiting enzyme that catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids, and the deletion or mutation of this gene can cause a significant decrease
in skin hair.
The study found that the expression of Scd1 changes
periodically during the cycle of hair growth.
When SCD1 is missing, the skin follicles are in a state of continuous elongation, and whether in the first hair growth cycle or shaving induced hair growth, the classic hair cycle morphological changes cannot be presented, causing hair follicle bulge formation disorders, which cannot provide a storage place
for resting HFSCs.
The study found that the hair loss caused by SCD1 deletion was not because it directly affected HFSCs, nor because it regulated mesenchymal cells and immune cells in the microenvironment, but because of the loss of
SCD1 in K14 keratinocytes 。 When SCD1 is missing in K14 keratinocytes, the expression of integrin) α6 on basal keratinocytes decreases significantly, resulting in a decrease in skin hemidesmosomeal structure assembly, excessive activation of the FAK-PI3K signaling pathway downstream of integrin, and promotion of proliferation and keratinization of keratinocytes, thereby inhibiting the shortening of hair follicles and outer root sheaths, and unable to form hair follicle bulge structure
。 By blocking PI3K overactivation or correcting SCD1-mediated fatty acid metabolism abnormalities with oleic acid, the hemidesmosomeal structure, hair follicle bulge structure, resting HFSCs and hair growth
of SCD1-deficient mice can be effectively restored.
This study discovered a novel mechanism by which fatty acid metabolism regulates HFSCs stem cell niche formation and homeostasis maintenance, which provides an important theoretical basis
for understanding hair growth and skin homeostasis maintenance.

Xue Yueqing, a doctoral graduate of the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, is the first author of the paper, and Professor Wang Ying and Shi Yufang are co-corresponding authors
.
This study was strongly supported
by Prof.
Kong Xiangyin and Prof.
Jun Qin from the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Prof.
Xinhua Liao from Shanghai University, and Prof.
Lydia Sorokin from the University of Münster, Germany.
Special thanks to Professor Zhang Xiaoren of Guangzhou Medical University and Professor Wang Honglin of the Institute of Immunology of Shanghai Jiao Tong University School of Medicine for their support and help
.
The research was supported by the National Key R&D Program of the Ministry of Science and Technology, the Strategic Pilot Project of the Chinese Academy of Sciences, the National Natural Science Foundation of China and the Chinese Academy of Sciences, as well as the public technology platform and animal platform of the Shanghai Institute of Nutrition and Health
, Chinese Academy of Sciences.

Schematic diagram of the molecular mechanism by which stearoyl-CoA desaturase 1 affects the formation of HFSCs-bulge

Article link: https://doi.
org/10.
1002/advs.
202201949