Transcription Factor DLX5 Promotes Hair Follicle Stem Cell Differentiation by Regulating the c-MYC/microRNA-29c-3p/NSD1 Axis.

Bojie Lin,Jiangying Zhu,Dan Huang,Siding Lu,Yuyong Yan,Guanyu Lin,Mingde Liao,Guoqian Yin

doi:10.3389/fcell.2021.554831

Abstract

IntroductionAdult stem cell function has been one of the most intensively explored areas of biological and biomedical research, with hair follicle stem cells serving as one of the best model systems. This study explored the role of the transcription factor DLX5 in regulating hair follicle stem cell (HFSC) differentiation.MethodsHFSCs were isolated, characterized, and assessed for their expression of DLX5, c-MYC, NSD1, and miR-29c-3p using RT-qPCR, Western blot analysis, or immunofluorescence. Next, the ability of HFSCs to proliferate as well as differentiate into either sebaceous gland cells or epidermal cells was determined. The binding of DLX5 to the c-MYC promoter region, the binding of c-MYC to the miR-29c-3p promoter region, and the binding of miR-29c-3p to the 3′-UTR of NSD1 mRNA were verified by luciferase activity assay and ChIP experiments.ResultsDLX5 was highly expressed in differentiated HFSCs. DLX5 transcriptionally activated c-MYC expression to induce HFSC differentiation. c-MYC was able to bind the miR-29c-3p promoter and thus suppressed its expression. Without miR-29c-3p mediated suppression, NSD1 was then able to promote HFSC differentiation. These in vitro experiments suggested that DLX5 could promote HFSC differentiation via the regulation of the c-MYC/miR-29c-3p/NSD1 axis.DiscussionThis study demonstrates that DLX5 promotes HFSC differentiation by modulating the c-MYC/miR-29c-3p/NSD1 axis and identifies a new mechanism regulating HFSC differentiation.

Highlights

Adult stem cell function has been one of the most intensively explored areas of biological and biomedical research, with hair follicle stem cells serving as one of the best model systems
The results of Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR), Western blot analysis and immunofluorescence assay suggested that the expression of DLX5 mRNA and protein was elevated in hair follicle stem cell (HFSC) differentiated cells compared with the undifferentiated control group (Figures 1D–F)
The results of RT-qPCR, Western blot analysis and immunofluorescence assay suggested that the expression levels of DLX5 mRNA and protein were increased in HFSCs differentiated cells compared with the undifferentiated control group (Figures 1H–J)

Summary

Introduction

Adult stem cell function has been one of the most intensively explored areas of biological and biomedical research, with hair follicle stem cells serving as one of the best model systems. This study explored the role of the transcription factor DLX5 in regulating hair follicle stem cell (HFSC) differentiation. DLX5 in HFSC Differentiation into multiple lineages (Wang et al, 2013; Shen et al, 2017). Their capacity to proliferate quickly makes HFSCs a potential source of stem cells used in cell therapies (Najafzadeh et al, 2015a). HFSCs have the ability to differentiate into multiple cell lineages, including hair follicle cells, keratinocyte cells, endothelial cells, sebaceous glands cells, and even neural cells (Najafzadeh et al, 2015b; Zhang et al, 2016; Joulai Veijouyeh et al, 2017; Quan et al, 2017). Promoting differentiation into these lineages in vitro and in vivo has been difficult

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