Defining Microrna Signatures of Hair Follicular Stem and Progenitor Cells in Healthy and Androgenic Alopecia Patients Publisher Pubmed



Mohammadi P^{1, 2, 3} ; Nilforoushzadeh MA⁴ ; Youssef KK⁵ ; Sharifizarchi A⁶ ; Moradi S¹ ; Khosravani P¹ ; Aghdami R^{1, 3} ; Taheri P¹ ; Hosseini Salekdeh G¹ ; Baharvand H^{1, 2} ; Aghdami N³
Source: Journal of Dermatological Science Published:2021

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. © 2020 Japanese Society for Investigative Dermatology