Tfap2b specifies an embryonic melanocyte stem cell that retains adult multifate potential.

Tfap2b specifies an embryonic melanocyte stem cell that retains adult multifate potential.
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DOI:
10.1016/j.celrep.2021.110234
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发表时间:
2022-01-11
期刊:
影响因子:
8.8
通讯作者:
Patton EE
Patton EE
中科院分区:
生物学1区
文献类型:
--
作者:
Brombin A;Simpson DJ;Travnickova J;Brunsdon H;Zeng Z;Lu Y;Young AIJ;Chandra T;Patton EE

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黑色素细胞是产生色素的细胞,由成体组织中的多个干细胞生态位补充。尽管色素沉着特征是黑色素瘤的已知危险因素,但我们对毛囊干细胞 (McSC) 以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 和研究其功能的关键谱系标记。在这里,我们发现 Tfap2b 和一组选定的靶基因指定了斑马鱼背根神经节的 McSC 群体。从功能上讲,Tfap2b 仅是少数晚期胚胎黑素细胞所必需的,并且对于 McSC 依赖性黑素细胞再生至关重要。命运图谱数据显示,tfap2b+ McSC 具有多重命运潜力,并且是大片成年黑色素细胞、其他两种色素细胞类型(虹膜细胞和黄色细胞)以及神经相关细胞的起源细胞。因此,Tfap2b 在早期发育中赋予 McSC 身份,将 McSC 与其他神经嵴和色素细胞谱系区分开来,并在成年斑马鱼中保留多命运潜力。 Tfap2b 及其靶基因指定具有混合色素细胞身份的 McSC 来自 McSC 的黑素细胞再生在功能上依赖于 Tfap2b tfap2b 指定干细胞生态位中的 ErbB 依赖性 McSC 命运图谱显示 Tfap2b-McSC 对成体色素细胞具有多重命运潜力 Brombin 等人。使用 scRNA 测序来鉴定斑马鱼 McSC 的转录组,并发现 tfap2b 是该细胞类型的功能标记。命运图谱分析表明,这些胚胎建立的干细胞在成年模式中具有多重命运的潜力。
Melanocytes, the pigment-producing cells, are replenished from multiple stem cell niches in adult tissue. 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 find that Tfap2b and a select set of target genes specify an McSC population at the dorsal root ganglia in zebrafish. Functionally, Tfap2b is required for only a few late-stage embryonic melanocytes, and is essential for McSC-dependent melanocyte regeneration. Fate mapping data reveal that tfap2b+ McSCs have multifate potential, and are the cells of origin for large patches of adult melanocytes, two other pigment cell types (iridophores and xanthophores), and nerve-associated cells. Hence, Tfap2b confers McSC identity in early development, distinguishing McSCs from other neural crest and pigment cell lineages, and retains multifate potential in the adult zebrafish. Tfap2b and its target genes specify McSCs with mixed pigment cell identities Melanocyte regeneration from McSCs functionally depends on Tfap2b tfap2b specifies ErbB-dependent McSCs at the stem cell niche Fate mapping reveals Tfap2b-McSCs have multifate potential for adult pigment cells Brombin et al. use scRNA sequencing to identify the transcriptome of McSCs in zebrafish and discover that tfap2b is a functional marker of this cell type. Fate mapping analyses reveal that these embryonically established stem cells have multifate potential in the adult pattern.
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