Cux1+ proliferative basal cells promote epidermal hyperplasia in chronic dry skin disease identified by single-cell RNA transcriptomics

Minhua Huang; Ning Hua; Siyi Zhuang; Qiuyuan Fang; Jiangming Shang; Zhen Wang; Xiaohua Tao; Jianguo Niu; Xiangyao Li; Peilin Yu; Wei Yang

doi:10.1016/j.jpha.2023.04.004

Cux1⁺ proliferative basal cells promote epidermal hyperplasia in chronic dry skin disease identified by single-cell RNA transcriptomics

J Pharm Anal. 2023 Jul;13(7):745-759. doi: 10.1016/j.jpha.2023.04.004. Epub 2023 Apr 11.

Authors

Minhua Huang¹, Ning Hua¹, Siyi Zhuang¹, Qiuyuan Fang¹, Jiangming Shang¹, Zhen Wang², Xiaohua Tao³, Jianguo Niu⁴, Xiangyao Li⁵, Peilin Yu⁶, Wei Yang^{1

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Affiliations

¹ Department of Biophysics, and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
² Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310000, China.
³ Department of Dermatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310000, China.
⁴ Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, 750000, China.
⁵ Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
⁶ Department of Toxicology, and Department of Medical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
⁷ MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, 310000, China.

Abstract

Pathological dry skin is a disturbing and intractable healthcare burden, characterized by epithelial hyperplasia and severe itch. Atopic dermatitis (AD) and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing (scRNA-seq). However, scRNA-seq analysis of the dry skin mouse model (acetone/ether/water (AEW)-treated model) is still lacking. Here, we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell (PBC) state that exclusively expresses transcription factor CUT-like homeobox 1 (Cux1). Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases (CDKs) and cyclins. Clinically, Cux1⁺ PBCs were increased in patients with psoriasis, suggesting that Cux1⁺ PBCs play an important part in epidermal hyperplasia. This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model, as well as a potential therapeutic target against dry skin-related dermatoses.

Keywords: Dry skin; Proliferative basal cells; scRNA-seq.