The Mesenchyme Command Factor y

Hair follicle loss is directly due to a decrease in the number of functioning dermal papilla cells, a stem cell group at the bottommost par t of our follicles. Dermal papilla cells are generated from hair follicle dermal stem cells (hfDSCs), a stem cell group capable of differentiating into both dermal papilla and dermal sheath cells. The dermal sheath surrounds the hair follicle, touching the dermal papilla in all hair cycles, while always separated from our outer root sheath cells (ORS) by the basement membrane formally titled the basal lamina.

Dynamic remodeling and morphology of the dermal sheath during the hair cycle During the growth phase (anagen), expanding DS tightly wraps the follicle and is closely juxtaposed with the epithelial ORS progenitors During the regression phase (catagen), the DS more loosely encases the epithelial strand around which restructuring of the basement membrane occurs (referred to as “glassy”) Apoptotic DS cells trail the regressing follicle in the DS “sleeve,” and by the resting phase (telogen), only a few DS cells persist and intimately surround the DP, which are bipotent stem cells termed hair follicle dermal stem cells (hfDSCs). Source: Rendl et. al (2020).

Throughout hair follicle cycles, there is a flow of mesenchyme stem cells between the dermal papilla and the dermal sheath. Jumpman outlined the flux between the two groups, discovering that both endothelin signalling (ET) and alpha smooth muscle actin (αSMA) act as pivotal pathways in the dermal sheath’s healthy contraction during catagen. Fur ther in catagen, Synthetic Pug presented that the senescence or displacement of dermal sheath cells may worsen the outflux of dermal papilla cells. Herber t shared terrific background of the two cell groups groups in several papers.

Ndimension highlighted that hair follicle dermal stem cells (hfDSCs) with upregulated levels of β-catenin experience senescence, leading us to question the long-term efficacy of the ever-mentioned Wnt pathway However, Jumpman, Herber t, and Tigris reminded us that DHT downregulates β-catenin and Wnt through DKK1–and perhaps additional inhibitors–posing that we need to only bring Wnt’s activation back to healthy levels Going beyond healthy Wnt levels results in senescence, as the body recognizes high levels as tumor growth and overactivates mTOR Much of our discussion on the dermal sheath’s role in hair follicle tissue remodeling remains open-ended

Contributors: Jumpman, Synthetic Pug, Ralf, Ndimension, Herber t, Tigris, Andy1, and Pubehead