Dicer- and Bulge Stem Cell-Dependent MicroRNAs During Induced Anagen Hair Follicle Development

Abstract

MicroRNAs (miRNAs) are a major class of conserved non-coding RNAs that have a wide range of functions during development and disease. Biogenesis of canonical miRNAs depend on the cytoplasmic processing of pre-miRNAs to mature miRNAs by the Dicer endoribonuclease. Once mature miRNAs are generated, the miRNAinduced silencing complex (miRISC), or miRISC, incorporates one strand of miRNAs as a template for recognizing complementary target messenger RNAs (mRNAs) to dictate post-transcriptional gene expression. Besides regulating miRNA biogenesis, Dicer is also part of miRISC to assist in activation of the complex. Dicer associates with other regulatory miRISC co-factors such as trans-activation responsive RNA-binding protein 2 (Tarbp2) to regulate miRNA-based RNA interference. Although the functional role of miRNAs within epidermal keratinocytes has been extensively studied within embryonic mouse skin, its contribution to the normal function of hair follicle bulge stem cells (BSCs) during post-natal hair follicle development is unclear. With this question in mind, we sought to ascertain whether Dicer-Tarpb2 plays a functional role within BSCs during induced anagen development by utilizing conditional knockout mouse models. Our findings suggest that Dicer, but not Tarbp2, functions within BSCs to regulate induced anagen (growth phase) development of post-natal hair follicles. These findings strengthen our understanding of miRNA-dependency within hair follicle cells during induced anagen development.

Reawakening GDNF's regenerative past in mice and humans

“…Interestingly, mammalian hair follicles go through cycles throughout adulthood that include phases of growth (anagen), regression (catagen), and rest (telogen), which mimics several embryonic processes [ 14 , 15 ]. During the anagen phase, the hair follicle's own elements are regenerated, which is controlled by many of the same signaling pathways as during morphogenesis [ 16 ].…”

“…During the anagen phase, the hair follicle's own elements are regenerated, which is controlled by many of the same signaling pathways as during morphogenesis [ 16 ]. Likewise, epithelial-mesenchymal communication is essential in postnatal cycling [ 14 ]. Signals from the mesenchymal dermal papilla to the epithelial stem cells initiate proper anagen entry, which then controls the proliferation and spatially ordered differentiation of transit-amplifying progenitor cells [ 17 , 18 ].…”

Stem cell‐intrinsic mechanisms regulating adult hair follicle homeostasis

“…Dicer is a riboendonuclease that regulates mature miRNA processing and facilitates post‐transcriptional gene silencing via miRNA‐induced silencing complex (miRISC) 148,149 . Recently, bulge specific ablation of Dicer has been found to cause HF differentiation defects following depilation induced anagen, likely due to decreased keratin expressions in HF layers 149 .…”

“…145,146 Combining the covalent ligation of endogenous Dicer is a riboendonuclease that regulates mature miRNA processing and facilitates post-transcriptional gene silencing via miR-NA-induced silencing complex (miRISC). 148,149 Recently, bulge specific ablation of Dicer has been found to cause HF differentiation defects following depilation induced anagen, likely due to decreased keratin expressions in HF layers. 149 Since ablation of another miRISC component Tarbp2 in bulge did not yield phenotypes observed in Dicer cKO HFs, the group speculated Dicer's miRNA processing function is necessary for proper HF development during anagen, where more miRNAs than previously thought might be involved.…”

DNA Damage-Induced Inflammatory Microenvironment and Adult Stem Cell Response

“…Kawase-Koga et al, 2010;Iliou et al, 2014;Park et al, 2017;Vishlaghi and Lisse, 2020;Gurung et al, 2021 …”