YAP signaling in horizontal basal cells promotes the regeneration of olfactory epithelium after injury

  • Stem Cell Reports. 2022 Mar 8;17(3):664-677. doi: 10.1016/j.stemcr.2022.01.007.
Qian Wu  1 ,  Xingxing Xu  2 ,  Xuemeng Miao  1 ,  Xiaomei Bao  2 ,  Xiuchun Li  3 ,  Ludan Xiang  4 ,  Wei Wang  4 ,  Siyu Du  4 ,  Yi Lu  4 ,  Xiwu Wang  2 ,  Danlu Yang  2 ,  Jingjing Zhang  2 ,  Xiya Shen  2 ,  Fayi Li  3 ,  Sheng Lu  3 ,  Yiren Fan  4 ,  Shujie Xu  4 ,  Zihao Chen  4 ,  Ying Wang  5 ,  Honglin Teng  6 ,  Zhihui Huang  7
Affiliations
  • 1. School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 2. School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 3. Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 4. School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 5. School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Department of Transfusion Medicine, Zhejiang Provincial People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310053, China. Electronic address: [email protected].
  • 6. Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: [email protected].
  • 7. School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: [email protected].
PMID: 35148842 DOI: 10.1016/j.stemcr.2022.01.007
Abstract

The horizontal basal cells (HBCs) of olfactory epithelium (OE) serve as reservoirs for stem cells during OE regeneration, through proliferation and differentiation, which is important in recovery of olfactory function. However, the molecular mechanism of regulation of HBC proliferation and differentiation after injury remains unclear. Here, we found that yes-associated protein (YAP) was upregulated and activated in HBCs after OE injury. Deletion of YAP in HBCs led to impairment in OE regeneration and functional recovery of olfaction after injury. Mechanically, YAP was activated by S1P/S1PR2 signaling, thereby promoting the proliferation of HBCs and OE regeneration after injury. Finally, activation of YAP signaling enhanced the proliferation of HBCs and improved functional recovery of olfaction after OE injury or in Alzheimer's disease model mice. Taken together, these results reveal an S1P/S1PR2/YAP pathway in OE regeneration in response to injury, providing a promising therapeutic strategy for OE injury.

Keywords
horizontal basal cells; olfactory epithelium; regeneration; yes-associated protein.
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