Dynamic regulation of chromatin accessibility during melanocyte stem cell activation

IF 3.9 3区 医学 Q2 CELL BIOLOGY Pigment Cell & Melanoma Research Pub Date : 2023-07-18 DOI:10.1111/pcmr.13112
Seoyeon Lee, Luye An, Paul D. Soloway, Andrew C. White
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Abstract

Melanocyte stem cells (McSCs) of the hair follicle are necessary for hair pigmentation and can serve as melanoma cells of origin when harboring cancer-driving mutations. McSCs can be released from quiescence, activated, and undergo differentiation into pigment-producing melanocytes during the hair cycle or due to environmental stimuli, such as ultraviolet-B (UVB) exposure. However, our current understanding of the mechanisms regulating McSC stemness, activation, and differentiation remains limited. Here, to capture the differing possible states in which murine McSCs can exist, we sorted melanocyte nuclei from quiescent (telogen) skin, skin actively producing hair shafts (anagen), and skin exposed to UVB. With these sorted nuclei, we then utilized single-nucleus assay for transposase-accessible chromatin with high-throughput sequencing (snATAC-seq) and characterized three melanocyte lineages: quiescent McSCs (qMcSCs), activated McSCs (aMcSCs), and differentiated melanocytes (dMCs) that co-exist in all three skin conditions. Furthermore, we successfully identified differentially accessible genes and enriched transcription factor binding motifs for each melanocyte lineage. Our findings reveal potential gene regulators that determine these melanocyte cell states and provide new insights into how aMcSC chromatin states are regulated differently under divergent intrinsic and extrinsic cues. We also provide a publicly available online tool with a user-friendly interface to explore this comprehensive dataset, which will provide a resource for further studies on McSC regulation upon natural or UVB-mediated stem cell activation.

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黑素细胞干细胞活化过程中染色质可及性的动态调节。
毛囊的黑色素细胞干细胞(McSC)是头发色素沉着所必需的,当携带癌症驱动的突变时,可以作为起源的黑色素瘤细胞。McSC可以在头发周期中或由于环境刺激(如紫外线-B(UVB)暴露)从静止状态释放、激活并分化为产生色素的黑素细胞。然而,我们目前对调节McSC干性、激活和分化的机制的理解仍然有限。在这里,为了捕捉小鼠McSC可能存在的不同可能状态,我们对静止(休止期)皮肤、活跃产生毛干的皮肤(生长期)和暴露于UVB的皮肤中的黑素细胞核进行了分类。利用这些分选的细胞核,我们利用单核分析法对转座酶可及的染色质进行高通量测序(snATAC-seq),并对三种黑素细胞谱系进行了表征:在所有三种皮肤条件下共存的静止型McSC(qMcSC)、活化型McSCs(aMcSC)和分化型黑素细胞(dMCs)。此外,我们成功地鉴定了每个黑素细胞谱系的差异可及基因,并富集了转录因子结合基序。我们的发现揭示了决定这些黑素细胞状态的潜在基因调节因子,并为aMcSC染色质状态如何在不同的内在和外在线索下受到不同调节提供了新的见解。我们还提供了一个具有用户友好界面的公开在线工具来探索这一全面的数据集,这将为进一步研究McSC对自然或UVB介导的干细胞激活的调节提供资源。
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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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