Defining microRNA signatures of hair follicular stem and progenitor cells in healthy and androgenic alopecia patients

J Dermatol Sci. 2021 Jan;101(1):49-57. doi: 10.1016/j.jdermsci.2020.11.002. Epub 2020 Nov 6.

Abstract

Background: The exact pathogenic mechanism causes hair miniaturization during androgenic alopecia (AGA) has not been delineated. Recent evidence has shown a role for non-coding regulatory RNAs, such as microRNAs (miRNAs), in skin and hair disease. There is no reported information about the role of miRNAs in hair epithelial cells of AGA.

Objectives: To investigate the roles of miRNAs affecting AGA in normal and patient's epithelial hair cells.

Methods: Normal follicular stem and progenitor cells, as well as follicular patient's stem cells, were sorted from hair follicles, and a miRNA q-PCR profiling to compare the expression of 748 miRNA (miRs) in sorted cells were performed. Further, we examined the putative functional implication of the most differentially regulated miRNA (miR-324-3p) in differentiation, proliferation and migration of cultured keratinocytes by qRT-PCR, immunofluorescence, and scratch assay. To explore the mechanisms underlying the effects of miR-324-3p, we used specific chemical inhibitors targeting pathways influenced by miR-324-3p.

Result: We provide a comprehensive assessment of the "miRNome" of normal and AGA follicular stem and progenitor cells. Differentially regulated miRNA signatures highlight several miRNA candidates including miRNA-324-3p as mis regulated in patient's stem cells. We find that miR-324-3p promotes differentiation and migration of cultured keratinocytes likely through the regulation of mitogen-activated protein kinase (MAPK) and transforming growth factor (TGF)-β signaling. Importantly, pharmacological inhibition of the TGF-β signaling pathway using Alk5i promotes hair shaft elongation in an organ-culture system.

Conclusion: Together, we offer a platform for understanding miRNA dynamic regulation in follicular stem and progenitor cells in baldness and highlight miR-324-3p as a promising target for its treatment.

Keywords: Androgenic alopecia; Hair follicular stem cells; miR-324-3p; miRNA.

MeSH terms

  • Adult
  • Alopecia / genetics*
  • Alopecia / pathology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Gene Expression Profiling
  • Hair Follicle / cytology
  • Hair Follicle / growth & development*
  • Humans
  • Keratinocytes
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Protein Kinase Inhibitors / pharmacology
  • Receptor, Transforming Growth Factor-beta Type I / antagonists & inhibitors
  • Receptor, Transforming Growth Factor-beta Type I / metabolism
  • Stem Cells / metabolism*
  • Transforming Growth Factor beta / metabolism

Substances

  • MIRN324 microRNA, human
  • MicroRNAs
  • Protein Kinase Inhibitors
  • Transforming Growth Factor beta
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human