Single-cell profiling reveals a potent role of quercetin in promoting hair regeneration.

Qian Zhao; Yandong Zheng; Dongxin Zhao; Liyun Zhao; Lingling Geng; Shuai MA; Yusheng Cai; Chengyu Liu; Yupeng Yan; Juan Carlos Izpisua Belmonte; Si Wang; Weiqi Zhang; Guang-hui Liu; Jing QU

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Single-cell profiling reveals a potent role of quercetin in promoting hair regeneration.

Author: Qian ZHAO ¹ ; Yandong ZHENG ² ; Dongxin ZHAO ³ ; Liyun ZHAO ¹ ; Lingling GENG ¹ ; Shuai MA ⁴ ; Yusheng CAI ⁴ ; Chengyu LIU ² ; Yupeng YAN ⁴ ; Juan Carlos Izpisua BELMONTE ⁵ ; Si WANG ¹ ; Weiqi ZHANG ⁶ ; Guang-Hui LIU ¹ ; Jing QU ²
Author Information

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. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
4. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
5. Altos Labs, Inc., San Diego, CA 94022, USA.
6. University of Chinese Academy of Sciences, Beijing 100049, China.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: HIF-1α; Que; endothelial cells; hair follicle regeneration; single-cell RNA-sequencing
MeSH: Mice; Animals; Quercetin/pharmacology*; Endothelial Cells; Hair; Hair Follicle; Alopecia
From: Protein & Cell 2023;14(6):398-415
CountryChina
Language:English
Abstract: 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.