Divergent proliferation patterns of distinct human hair follicle epithelial progenitor niches in situ and their differential responsiveness to prostaglandin D2

Abstract

Human scalp hair follicles (hHF) harbour several epithelial stem (eHFSC) and progenitor cell sub-populations organised into spatially distinct niches. However, the constitutive cell cycle activity of these niches remains to be characterized in situ. Therefore, the current study has studied these characteristics of keratin 15+ (K15), CD200+ or CD34+ cells within anagen VI hHFs by immunohistomorphometry, using Ki-67 and 5-ethynyl-2′-deoxyuridine (EdU). We quantitatively demonstrate in situ the relative cell cycle inactivity of the CD200+/K15+ bulge compared to other non-bulge CD34+ and K15+ progenitor compartments and found that in each recognized eHFSC/progenitor niche, proliferation associates negatively with eHFSC-marker expression. Furthermore, we also show how prostaglandin D2 (PGD2), which is upregulated in balding scalp, differentially impacts on the proliferation of distinct eHFSC populations. Namely, 24 h organ-cultured hHFs treated with PGD2 displayed reduced Ki-67 expression and EdU incorporation in bulge resident K15+ cells, but not in supra/proximal bulb outer root sheath K15+ progenitors. This study emphasises clear differences between the cell cycle behaviour of spatially distinct stem/progenitor cell niches in the hHF, and demonstrates a possible link between PGD2 and perturbed proliferation dynamics in epithelial stem cells.

CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane‐induced alopecia

“…by promoting chromosome missegregation/cell division on multipolar spindles (Chen & Horwitz, ; Abal et al , ; Morse et al , ; Weaver, ; Zasadil et al , ). Taxanes are thus presumed to cause hair loss by damaging rapidly dividing matrix keratinocytes and their counterpart stem/progenitor cells, required for healthy hair growth and hair follicle cycling (Paus & Cotsarelis, ; Garza et al , ; Paus et al , ; Purba et al , , ,b; Gao et al , ; Huang et al , ). However, the effects of taxane chemotherapy on the human hair follicle remain to be systematically examined.…”

Visualization of Global RNA Synthesis in a Human (mini-) Organ in Situ by Click Chemistry

“…Analysis of EU signal within eSC-containing compartments of the ORS (i.e.,bulge, sub-bulge and proximal bulb ORS) [8] unexpectedly showed reduced and heterogeneous patterns of RNA synthesis, relative to MKs, which displayed maximal EU fluorescence (Figure 1B). Comparative analysis of EU incorporation within the matrix, pre-cortex, IRS and DP of the HF bulb [9,10] showed relative compartmental homogeneity in levels of RNA synthesis, as no significant differences in EU signal were seen between these cell populations (Figure 1CD).…”

“…As regions of ORS cells were clearly transcriptionally inactive (Figure 1A), it was hypothesized that EU incorporation would negatively associate with eSC marker K15, as observed with proliferation [8]. By analyzing EU incorporation into basal K15 + cells versus K15 - suprabasal ORS cells, no correlation was found between the expression of the eSC marker K15 with EU staining (Figure 2A).…”

“… (A) Analysis of EU signal within K15 + and K15 - cells within the human HF bulge [8]. Statistical analysis (Mann-Whitney U test) performed on regional values obtained from 15 HFs from four patients; no significant difference was found.…”

“…Statistical analysis (Mann-Whitney U test) performed on regional values obtained from 15 HFs from four patients; no significant difference was found. (B) Analysis of EU signal within Ki-67 + and Ki-67 - cells within proliferative ORS regions of the human HF [8]. Statistical analysis (Mann-Whitney U test) performed on regional values obtained from 12 HFs from four patients; no significant difference was found.…”