TY - JOUR
T1 - Divergent proliferation patterns of distinct human hair follicle epithelial progenitor niches in situ and their differential responsiveness to prostaglandin D2
AU - Purba, Talveen S.
AU - Peake, Michael
AU - Farjo, Bessam
AU - Farjo, Nilofer
AU - Bhogal, Ranjit K.
AU - Jenkins, Gail
AU - Paus, Ralf
N1 - Funding Information:
We thank Derek Pye and Stella Pearson for excellent technical support. This work was supported by a BBSRC-Unilever iCASE PhD studentship (recipient: T.P.; award: R.P.) and the “Inflammatory Hair Diseases” programme of the NIHR Manchester Biomedical Research Centre (R.P.). Kayumba Ng’andu is thanked for proofreading of the manuscript.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-017-15038-9
DO - 10.1038/s41598-017-15038-9
M3 - Article
C2 - 29123134
AN - SCOPUS:85033705034
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 15197
ER -