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人类表皮干细胞的分化受特定脂质亚种的调节。

Human epidermal stem cell differentiation is modulated by specific lipid subspecies.

机构信息

Centre for Stem Cells and Regenerative Medicine, King's College London, SE1 9RT London, United Kingdom.

European Bioinformatics Institute, CB10 1SD Hinxton, United Kingdom.

出版信息

Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22173-22182. doi: 10.1073/pnas.2011310117. Epub 2020 Aug 25.

DOI:10.1073/pnas.2011310117
PMID:32843345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7486749/
Abstract

While the lipids of the outer layers of mammalian epidermis and their contribution to barrier formation have been extensively described, the role of individual lipid species in the onset of keratinocyte differentiation remains unknown. A lipidomic analysis of primary human keratinocytes revealed accumulation of numerous lipid species during suspension-induced differentiation. A small interfering RNA screen of 258 lipid-modifying enzymes identified two genes that on knockdown induced epidermal differentiation: , encoding elongation of very long-chain fatty acids protein 1, and , encoding fatty acid transport protein 1. By intersecting lipidomic datasets from suspension-induced differentiation and knockdown keratinocytes, we pinpointed candidate bioactive lipid subspecies as differentiation regulators. Several of these-ceramides and glucosylceramides-induced differentiation when added to primary keratinocytes in culture. Our results reveal the potential of lipid subspecies to regulate exit from the epidermal stem cell compartment.

摘要

尽管哺乳动物表皮外层的脂质及其对屏障形成的贡献已被广泛描述，但单个脂质种类在角质形成细胞分化中的作用仍不清楚。对原代人角质形成细胞的脂质组学分析显示，在悬浮诱导分化过程中会积累许多脂质种类。对 258 种脂质修饰酶的小干扰 RNA 筛选鉴定出两种在敲低后诱导表皮分化的基因：编码长链脂肪酸延长酶 1 的 和编码脂肪酸转运蛋白 1 的 。通过将悬浮诱导分化和敲低角质形成细胞的脂质组学数据集进行交集，我们确定了候选生物活性脂质亚类作为分化调节剂。当将其中几种——神经酰胺和葡萄糖神经酰胺添加到培养的原代角质形成细胞中时，它们会诱导分化。我们的结果揭示了脂质亚类调节表皮干细胞区室退出的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/abf52d4b41e8/pnas.2011310117fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/0168b87bba01/pnas.2011310117fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/b723258e0aea/pnas.2011310117fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/c7efa9e71b16/pnas.2011310117fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/abf52d4b41e8/pnas.2011310117fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/0168b87bba01/pnas.2011310117fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/b723258e0aea/pnas.2011310117fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/c7efa9e71b16/pnas.2011310117fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5e/7486749/abf52d4b41e8/pnas.2011310117fig04.jpg

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