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

单细胞 RNA 转录组学鉴定出 Cux1+ 增殖基底细胞促进慢性干性皮肤病中的表皮增生

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

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.

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