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首页> 外文期刊>Pigment cell research >Both Notch1 and Notch2 contribute to the regulation of melanocyte homeostasis
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Both Notch1 and Notch2 contribute to the regulation of melanocyte homeostasis

机译：Notch1和Notch2均有助于调节黑色素细胞稳态

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摘要

Notch signaling affects a variety of mammalian stem cells, but there has been limited evidence that a specific Notch molecule regulates adult stem cells. Recently, it was reported that the reduced Notch signaling initiated at the embryonic stage results in a gradual hair graying phenotype after birth. Here we demonstrate that the oral administration of a γ-secretase inhibitor (GSI) to wild-type adult C57/Bl6 mice led to a gradual increase in gray spots, which remained unchanged for at least 20 weeks after discontinuing the GSI. In GSI-treated mice, there was a severe decrease in unpigmented melanocytes in the bulge/subbulge region where melanocyte stem cells are located. While we confirmed that Notch1+/?Notch2+/? double heterozygous mice with a C57/Bl6 background were born with a normal hair color phenotype and gradually turned gray after the second hair cycle, in the c-kit mutant Wv background, Notch1+/? and Notch2+/? mice had larger white spots on the first appearance of hair than did the Wv/+ mice, which did not change throughout life. Notch1+/?Notch2+/?Wv/+ mice had white hair virtually all over the body at the first appearance of hair and the depigmentation continued to progress thereafter. Using a neural crest organ culture system, GSI blocked the generation of pigmented melanocytes when added to the culture during the period of melanoblast proliferation, but not during the period of differentiation. These observations imply roles of Notch signaling in both development of melanocyte during embryogenesis and maintenance of melanocyte stem cells in adulthood, while the degree of requirement is distinct in these settings: the latter is more sensitive than the former to the reduced Notch signaling. Furthermore, Notch1 and Notch2 cooperates with c-kit signaling during embryogenesis, and they cooperate with each other to regulate melanocyte homeostasis after birth.
机译：Notch信号传导影响多种哺乳动物干细胞，但有限的证据表明特定的Notch分子调节成年干细胞。近来，据报道，在胚胎期开始的Notch信号传导减少导致出生后头发逐渐变白的表型。在这里，我们证明了向野生型成年C57 / Bl6小鼠口服γ-分泌酶抑制剂（GSI）导致灰点逐渐增加，在中断GSI后至少20周内保持不变。在用GSI处理的小鼠中，黑色素干细胞所在的隆起/亚隆起区域的未色素沉着黑色素细胞严重减少。虽然我们确认Notch1 + /？在C-kit突变Wv背景Notch1 + /？中，具有C57 / Bl6背景的双杂合子小鼠出生时具有正常的头发颜色表型，并且在第二个头发周期后逐渐变成灰色。和Notch2 + /？与Wv / +小鼠相比，小鼠在毛发初次出现时具有较大的白斑，而Wv / +小鼠在整个生命中都不会改变。在第一次出现毛发时，Notch1 + /ΔNotch2+ /ΔWv/ +小鼠实际上遍布全身白发，其后脱色继续进行。使用神经c器官培养系统，当在黑素母细胞增殖期间（而不是分化期间）添加到培养物中时，GSI阻止了有色黑色素细胞的生成。这些观察结果表明，Notch信号在胚胎形成过程中的黑素细胞发育和成年期黑素细胞干细胞的维持中均起着作用，而在这些情况下需求的程度是不同的：后者对减少的Notch信号更敏感。此外，Notch1和Notch2在胚胎发生过程中与c-kit信号传导协同作用，并且彼此协同作用以调节出生后黑素细胞的稳态。

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