Indispensable role of Bcl2 in the development of the melanocyte stem cell
Indispensable role of Bcl2 in the development of the melanocyte stem cell
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DOI：
10.1016/j.ydbio.2005.12.025
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发表时间：
2006-03-01
影响因子：
2.7
通讯作者：
Nishikawa, S
中科院分区：
文献类型：
--
作者：
Mak, SS;Moriyama, M;Nishikawa, S
Bcl 2基因敲除小鼠表现出色素沉着的特征性丧失，证明了Bcl 2在黑素细胞（Me）谱系中的重要性。最近报道，这种异常表型是由于黑素细胞干细胞（MSC）维持的失败，并且Bcl 2对于MSC的存活是选择性重要的。然而，在我们对同一只小鼠的分析中，我们观察到表皮和滤泡群体中的成黑色素细胞（Mb）数量减少。更重要的是，没有MSC。表皮中的SCF下调伴随着在Bcl 2缺失中观察到的Mb数量的急剧减少，表明Bcl 2对于在不存在c-Kit信号传导的情况下Mb的存活是不可缺少的。因此，在Bcl 2缺失小鼠中废除c-Kit信号传导耗尽所有Mb和Mcs，而在表皮角质形成细胞中持续表达SCF拯救MSC。我们的研究结果表明，Bcl 2在Mb和Me存活中具有普遍作用，并且对于MSC的出现至关重要。此外，结果表明，提供毛发色素沉着的第一波MC直接来源于绕过MSC的表皮Mbs。此外，揭示了SCIF在Mc谱系中的Bcl 2非依赖性作用机制，因为SCIF c-Kit信号传导在不存在Bcl 2的情况下是功能性的。(c)2005年爱思唯尔公司All rights reserved.
Bcl2 null mice display a characteristic loss of pigmentation demonstrating the importance of Bcl2 in the melanocyte (Me) lineage. It was recently reported that this abnormal phenotype is due to the failure of melanocyte stem cell (MSC) maintenance and that Bcl2 is selectively important for the survival of MSCs. However, in our analysis of the same mouse, we observe a reduction in nielanoblast (Mb) number in both epidermal and follicular populations. More importantly, there is a complete absence of MSCs. SCF down regulation in the epidermis is concomitant with the dramatic reduction in Mb numbers observed in the Bcl2 null, suggesting that Bcl2 is indispensable for the survival of Mbs in the absence of c-Kit signaling. Consistently, abrogation of c-Kit signaling in Bcl2 null mice depletes all Mbs and Mcs, whereas continuous expression of SCF in epidermal keratinocytes rescues the MSCs. Our results demonstrate that Bcl2 has a general role in Mb and Me Survival and is essential for the emergence of MSCs. Moreover, the results indicate that the first wave of Mcs that provide hair pigmentation is derived directly from epidermal Mbs bypassing MSCs. Furthermore, a Bcl2-independent mechanism of action of SCIF in the Mc lineage is revealed as SCIF c-Kit signaling is functional in the absence of Bcl2. (c) 2005 Elsevier Inc. All rights reserved.