Single-cell profiling reveals a potent role of quercetin in promoting hair regeneration
Qian Zhao1,2, Yandong Zheng3,4, Dongxin Zhao11, Liyun Zhao1,2, Lingling Geng1,2, Shuai Ma5,6,7, Yusheng Cai5,6,7, Chengyu Liu3,4, Yupeng Yan5,6,7, Juan Carlos Izpisua Belmonte12, Si Wang1,2,10(), Weiqi Zhang4,6,7,8,9(), Guang-Hui Liu1,2,4,5,6,7(), Jing Qu3,4,6,7()
1. Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China 2. Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China 3. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China 4. University of Chinese Academy of Sciences, Beijing 100049, China 5. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China 6. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China 7. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China 8. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing 100101, China 9. Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China 10. The Fifth People’s Hospital of Chongqing, Chongqing 400062, China 11. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China 12. Altos Labs, Inc., San Diego, CA 94022, USA
Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
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