Human Epithelial Stem Cell Survival Within Their Niche Requires Tonic Cannabinoid Receptor 1 Signaling—Lessons From the Hair Follicle

February 2021 in “ Experimental Dermatology ”

Koji Sugawara, Nóra Zákány, Stephan Tiede, Talveen S. Purba, Matthew Harries, Daisuke Tsuruta, Tamás Bı́ró, Ralf Paus

Studysummary This study found that activating CB1 receptor signaling in human hair follicles increased stem cell proliferation while reducing differentiated cell survival, suggesting CB1's role as a survival stimulus for epithelial stem cells. Our plain-language summary of this paper — not a Tressless recommendation.

The study demonstrated that selective activation of cannabinoid receptor-1 (CB1) signaling via the MAPK and Akt pathways significantly increased the number and proliferation of cytokeratin CK15+ or CK19+ human hair follicle (HF) bulge epithelial stem cells (eSCs) and enhanced CK15 promoter activity. Conversely, CB1 stimulation promoted apoptosis in the differentiated progeny of these eSCs. CB1 gene knockdown or antagonist treatment reduced HF eSC numbers and stimulated their apoptosis, while CB1 knockout mice showed a reduced bulge eSC pool. This indicated that "tonic" CB1 signaling was essential for the survival of adult human HF eSCs within their niche, a crucial consideration for therapeutic targeting of the human endocannabinoid system.

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