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

The study investigated the expression patterns of transcription factors LHX2 and SOX9 in human hair follicles, particularly in relation to known epithelial hair follicle stem cell markers K15 and K19. It was found that K15 and K19 marked distinct progenitor cell populations in different regions of the outer root sheath (ORS), with K19 expression stronger in the proximal bulb ORS and K15 stronger in the bulge. LHX2 and SOX9 were distributed throughout the ORS, not limited to the bulge, with SOX9 most prominent below the bulge and LHX2 between the sub-bulge and proximal bulb ORS. During catagen, LHX2 and SOX9 expression increased in the proximal HF epithelium. The study concluded that LHX2 and SOX9 identify distinct progenitor cell populations, separate from K15 and K19, potentially playing a crucial role in maintaining the human hair follicle epithelium.

The study explored the role of cannabinoid receptor 1 (CB1) in regulating keratin expression in human skin, particularly focusing on keratins K6 and K16, which are up-regulated in psoriasis. Researchers found that activating CB1 with the agonist ACEA reduced the expression of K6 and K16 in human skin and cultured keratinocytes, effects that were partially reversed by the CB1 antagonist AM251. This reduction in keratin expression was independent of CB1's anti-proliferative effects on keratinocytes. The findings suggested that CB1-mediated signaling could be a novel mechanism for controlling keratin expression, with potential implications for psoriasis treatment and wound healing.