Targeted Knockout of β-Catenin in Adult Melanocyte Stem Cells Using a Mouse Line, Dct::CreER T2, Results in Disrupted Stem Cell Renewal and Pigmentation Defects
Targeted Knockout of β-Catenin in Adult Melanocyte Stem Cells Using a Mouse Line, Dct::CreER T2, Results in Disrupted Stem Cell Renewal and Pigmentation Defects
复制标题
使用小鼠品系 Dct::CreER T2 靶向敲除成体黑素细胞干细胞中的 β-连环蛋白，导致干细胞更新中断和色素沉着缺陷
DOI：
10.1016/j.jid.2020.08.025
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Larue L.
中科院分区：
文献类型：
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作者：
Le Coz M;Aktary Z;Watanabe N;Yajima I;Pouteaux M;Charoenchon N;Motohashi T;Kunisada T;Corvelo A;Larue L.
黑素细胞（MC）是主要在表皮和毛囊（HF）中发现的色素产生细胞，在那里它们将黑色素转移到内毛干中的角质形成细胞（科隆博等人，2011年）。Mc祖细胞，即成黑素细胞，在胚胎发生期间从神经嵴细胞产生，沿胚胎沿着迁移，并定殖于表皮和HF（Petit和Larue，2016; Vandamme和Berx，2019）。在HF中，成熟的MC在球中发现，而MC干细胞（McSC）在隆突中发现（Nishimura et al.，2002; Osawa等人，2005年; Vandamme和Berx，2019年）。在Mc更新过程中，在隆起的McSCs逃脱静止增殖，形成过境扩增细胞，迁移下来的HF和到达灯泡作为完全成熟的Mcs. CreER T2系统，它允许Cre/loxP介导的位点特异性重组，允许有效和准确的时间操纵基因的组织特异性和条件的方式。Tyr：：CreER T2-Bos小鼠先前用于靶向McSC，这是有争议的，因为酪氨酸酶（Tyr）在McSC中不表达（Mort et al.，2015; Nishimura，2011; Osawa等人，2005），并且因为这些小鼠中CreER T2酶的活性在出生后3天开始的隆起中的黑素细胞中基本上不存在（Harris和Pavan，2013）。因此，不清楚McSC表达Tyr的比例（如果有的话）以及何时表达。因此，尽管Tyr：：CreER T2-Bos小鼠可用于研究McSC，但它们可能不是最佳的。
Melanocytes (Mcs) are pigment-producing cells primarily found in the epidermis and hair follicles (HFs), where they transfer melanin to keratinocytes in the inner hair shaft (Colombo et al., 2011). Mc progenitor cells, melanoblasts, arise from neural crest cells during embryogenesis, migrate along the embryo, and colonize the epidermis and HFs (Petit and Larue, 2016; Vandamme and Berx, 2019). In the HF, mature Mcs are found in the bulb, whereas Mc stem cells (McSCs) are found in the bulge (Nishimura et al., 2002; Osawa et al., 2005; Vandamme and Berx, 2019). During Mc renewal, McSCs in the bulge escape quiescence to proliferate, forming transit amplifying cells, which migrate down the HF and arrive at the bulb as fully mature Mcs.The CreER T2 system, which allows for Cre/loxP-mediated site-specific recombination, permits the effective and accurate temporal manipulation of genes in a tissue-specific and conditional manner. Tyr:: CreER T2-Bos mice were previously used for targeting McSCs, which is controversial because tyrosinase (Tyr) is not expressed in McSCs (Mort et al., 2015; Nishimura, 2011; Osawa et al., 2005) and because the activity of the CreER T2 enzyme in these mice is essentially absent in melanocytic cells in the bulge starting after 3 days after birth (Harris and Pavan, 2013). Therefore, it is unclear what proportion, if any, of McSCs express Tyr and when. As such, whereas Tyr:: CreER T2-Bos mice can be used to study McSCs, they are perhaps not optimal.