Self-renewal and multilineage differentiation of mouse dental epithelial stem cells.
Self-renewal and multilineage differentiation of mouse dental epithelial stem cells.
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DOI：
10.1016/j.scr.2013.06.008
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发表时间：
2013-11
影响因子：
1.2
通讯作者：
Wang, Fen
中科院分区：
文献类型：
--
作者：
Chang, Julia Yu Fong;Wang, Cong;Jin, Chengliu;Yang, Chaofeng;Huang, Yanqing;Liu, Junchen;McKeehan, Wallace L.;D'Souza, Rena N.;Wang, Fen
了解支持小鼠门牙无限生长潜能的牙上皮干细胞（DESCs）自我更新和分化的细胞和分子机制，对于开发新的牙齿再生疗法和揭示牙源性肿瘤的发病机制至关重要。然而，DESC特性和调控的分析一直受到缺乏体外测定系统和充分记录的DESC标记物的限制。在这里，我们描述了一个体外球体培养系统，从出生后的小鼠门牙颈环（CLs）中分离DESCs，其中DESCs被认为存在。在培养系统中，离体细胞能够扩增并形成多代球。谱系示踪表明，球内DESC起源于上皮细胞。刺激后，球细胞分化为表达角蛋白14和淀粉原蛋白的细胞和产生矿物物质的细胞。与CL组织相比，球细胞表达高水平的Sca-1、CD49f（也称为整合素α6）和CD44。小鼠切牙CL细胞的荧光活化细胞分选（FACS）分析进一步表明，CD49fBright群体在球形细胞中富集。此外，CD49fBright群体包括慢循环和Lgr5+ desc。体外球培养系统和CD49fBright作为DESC标记物的鉴定为DESC的富集、DESC的维持、细胞命运决定和分化调控以及牙齿再生疗法的发展提供了一个新的平台。
Understanding the cellular and molecular mechanisms underlying the self-renewal and differentiation of dental epithelial stem cells (DESCs) that support the unlimited growth potential of mouse incisors is critical for developing novel tooth regenerative therapies and unraveling the pathogenesis of odontogenic tumors. However, analysis of DESC properties and regulation has been limited by the lack of an in vitro assay system and well-documented DESC markers. Here, we describe an in vitro sphere culture system to isolate the DESCs from postnatal mouse incisor cervical loops (CLs) where the DESCs are thought to reside. The dissociated cells from CLs were able to expand and form spheres for multiple generations in the culture system. Lineage tracing indicated that DESC within the spheres were epithelial in origin as evident by lineage tracing. Upon stimulation, the sphere cells differentiated into cytokeratin 14- and amelogenin-expressing and mineral material-producing cells. Compared to the CL tissue, sphere cells expressed high levels of expression of Sca-1, CD49f (also designated as integrin α6), and CD44. Fluorescence-activated cell sorting (FACS) analyses of mouse incisor CL cells further showed that the CD49fBright population was enriched in sphere-forming cells. In addition, the CD49fBright population includes both slow-cycling and Lgr5+ DESCs. The in vitro sphere culture system and identification of CD49fBright as a DESC marker provide a novel plateform for enriching DESCs, interrogating how maintenance, cell fate determination, and differentiation of DESCs are regulated, and developing tooth regenerative therapies.
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影响因子：
64.8
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