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双联抗血小板治疗在控制人毛囊干细胞增殖与分化中的作用

DAPT in the control of human hair follicle stem cell proliferation and differentiation.

作者信息

Jiang Jindou, Miao Yong, Xiao Shune, Zhang Zhidan, Hu Zhiqi

机构信息

Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, China. Head of Department: Jianhua Gao.

出版信息

Postepy Dermatol Alergol. 2014 Aug;31(4):201-6. doi: 10.5114/pdia.2014.44002. Epub 2014 Aug 22.

Abstract

INTRODUCTION

Stem cells from hair follicle have great therapeutic applications in regenerative medicine as sources of cells for transplantation. The differentiation pathway selected by hair follicle stem cells (HFSC) is largely determined by local microenvironmental signals. In this study, human hair follicle stem cells were treated with Notch signaling blocker to explore a new approach to modulate human hair follicle stem cell proliferation and differentiation in vitro.

AIM

To define the functional consequences of blocking the Notch signaling pathway on the proliferation and differentiation of human HSCs.

MATERIAL AND METHODS

The human hair follicle stem cells were treated with various concentrations of Notch signaling blocker DAPT (24-diamino-5-phenylthiazole). The viability of the cells was investigated with clonogenicity assays. The expression of stem cell markers, cell cycle and cell apoptosis were analysed by flow cytometry.

RESULTS

Notch blocking leads to promotion of human hair follicle stem cell proliferation and inhibition of differentiation in response to DAPT. The maximum effect of DAPT on the viability of human HFSC was observed at a concentration of 20 µM. We found that DAPT treatment results in downregulation of Hes1 and p21 and upregulation of Wnt10b.

CONCLUSIONS

γ-Secretase inhibitor DAPT has a modulatory effect on the human HFSC. The DAPT may modulate human hair follicle stem cell proliferation and differentiation through regulation of p21 and Wnt-10b.

摘要

引言

毛囊干细胞在再生医学中作为移植细胞来源具有巨大的治疗应用价值。毛囊干细胞(HFSC)选择的分化途径很大程度上由局部微环境信号决定。在本研究中,用人Notch信号阻滞剂处理人毛囊干细胞,以探索一种在体外调节人毛囊干细胞增殖和分化的新方法。

目的

确定阻断Notch信号通路对人毛囊干细胞增殖和分化的功能影响。

材料和方法

用人Notch信号阻滞剂DAPT(2-氨基-5-苯基噻唑)的不同浓度处理人毛囊干细胞。通过克隆形成试验研究细胞活力。通过流式细胞术分析干细胞标志物的表达、细胞周期和细胞凋亡。

结果

Notch阻断导致人毛囊干细胞增殖增加以及对DAPT反应的分化受到抑制。在20μM浓度下观察到DAPT对人毛囊干细胞活力的最大作用。我们发现DAPT处理导致Hes1和p21下调以及Wnt10b上调。

结论

γ-分泌酶抑制剂DAPT对人毛囊干细胞有调节作用。DAPT可能通过调节p21和Wnt-10b来调节人毛囊干细胞的增殖和分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c9/4171676/07b40ebf8129/PDIA-31-23136-g001.jpg

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