Identification of hair shaft progenitors that create a niche for hair pigmentation

Abstract

Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20 + cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes.

Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials

“…Foxn1‐positive hair cortex epithelial progenitors secrete Fgf2 which instructs melanocytes to produce and transmit melanin to the epithelial cells . Both Foxn1 and Krox20 are regulated by Wnt/β‐catenin signalling . This further indicates that Wnt signalling is indispensable for activation and differentiation of McSCs during initiation and progression of the hair cycle.…”

“…Yet melanocytes only produce and transmit melanin to the hair cortex and medulla. Krox20‐positive hair matrix progenitors regulate melanocyte differentiation and hair pigmentation by secreting SCF . Foxn1‐positive hair cortex epithelial progenitors secrete Fgf2 which instructs melanocytes to produce and transmit melanin to the epithelial cells .…”

Prevention of graying: Is KROX20 the solution?

“…Removal of SCF from the KROX20 cells causes complete pigment loss as the hair cycles. Additionally, Liao et al () also proved that the KROX20+ cells originate from a Keratin 14+ keratinocyte lineage and that KROX20 expression starts later in hair follicle development. While critical to hair pigmentation, KROX20 cells were also shown to be critical for overall hair growth as KROX20 cell depletion caused shrunken hair bulbs and subsequently the inability to grow new hair.…”

“…A recent article by Liao et al (Liao, Booker, Morrison, & Le, ) sheds new light on hair graying. KROX20 is a zinc finger transcription factor implicated in myelination and immune responses, but has also been noted to be expressed in subpopulations of cells in the hair follicle.…”

Identifying the niche controlling melanocyte differentiation

“…Despite the well-characterized function of the SCF/c-Kit signaling pathway in regulating melanocyte differentiation, the cellular source of SCF and the niche involved in melanocyte differentiation and hair pigmentation remain elusive. In this issue of Genes & Development, Liao et al (2017) report the identification of the progeny of hair shaft progenitors expressing the transcription factor Krox20 as the source of Scf required for melanocyte differentiation and forming the niche required for hair pigmentation (Fig. 1).…”