Tfap2b specifies an embryonic melanocyte stem cell that retains adult multi-fate potential
Tfap2b specifies an embryonic melanocyte stem cell that retains adult multi-fate potential
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DOI：
10.1101/2021.06.18.448859
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
A. Brombin;Daniel J. Simpson;J. Travnickova;Hannah Brunsdon;Zhiqiang Zeng;Yuting Lu;Adelaide I.J. Young;Tamir Chandra;E. Patton
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作者：
A. Brombin;Daniel J. Simpson;J. Travnickova;Hannah Brunsdon;Zhiqiang Zeng;Yuting Lu;Adelaide I.J. Young;Tamir Chandra;E. Patton
黑色素细胞，我们的色素生成细胞，是从成人组织中的多个干细胞龛中补充的。虽然色素沉着特征是已知的黑色素瘤的危险因素，但我们对除毛囊外的黑素细胞干细胞（McSC）群体知之甚少，并且缺乏用于识别McSC并研究其功能的关键谱系标记。在这里，我们发现Tfap2b及其一组精选的靶基因指定了斑马鱼背根神经节的McSC群体。功能上，Tfap2b仅在少数晚期胚胎黑素细胞中是必需的，而在mcc依赖性黑素细胞再生中却是必需的。命运图谱数据显示，表达tfap2b的McSCs具有多种命运潜能，并且是成年黑色素细胞和其他两种色素细胞类型（虹膜细胞和黄细胞）的起源细胞。因此，Tfap2b在早期发育中赋予McSC身份，从而将McSC与其他神经嵴和色素细胞系区分开来，并在成年斑马鱼中保留多种命运潜力。强调Tfap2b及其靶基因指定具有混合色素细胞身份的McSCs，其功能依赖于Tfap2b从McSC中再生黑素细胞，Tfap2b在干细胞生态位指定erbb依赖性McSCs，命运定位显示Tfap2b-McSCs具有成人色素细胞的多重命运潜力
Melanocytes, our pigment producing cells, are replenished from multiple stem cell niches in adult tissues. Although pigmentation traits are known risk-factors for melanoma, we know little about melanocyte stem cell (McSC) populations other than hair follicle McSCs, and lack key lineage markers with which to identify McSCs and study their function. Here, we discover that Tfap2b, and a select set of its target genes, specifies an McSC population at the dorsal root ganglia in zebrafish. Functionally, Tfap2b is required for only a few late-stage embryonic melanocytes, and instead is essential for McSC-dependent melanocyte regeneration. Fate- mapping data reveal that tfap2b-expressing McSCs have multi-fate potential, and are the cell-of- origin for large patches of adult melanocytes, and two other pigment cell types, iridophores and xanthophores. Hence, Tfap2b confers McSC identity in early development, thereby distinguishing McSCs from other neural crest and pigment cell lineages, and retains multi-fate potential in the adult zebrafish. Highlights Tfap2b and its target genes specify McSCs with mixed pigment cell identities Functional dependence on Tfap2b for melanocyte regeneration from the McSC tfap2b specifies ErbB-dependent McSCs at the stem cell niche Fate mapping reveals Tfap2b-McSCs have multi-fate potential for adult pigment cells