Dynamic Changes in the Gene Expression Patterns and Lipid Profiles in the Developing and Maturing Meibomian Glands.

Dynamic Changes in the Gene Expression Patterns and Lipid Profiles in the Developing and Maturing Meibomian Glands.
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DOI:
10.3390/ijms23147884
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发表时间:
2022-07-17
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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--
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睑板腺(MG)及其全分泌分泌物-睑脂-在眼睛的生理学中起着至关重要的作用,提供保护免受环境因素和干燥,以及其他功能。重要的是,衰老与MG的形态和功能以及它们产生的睑脂的数量和质量的恶化有关,导致其保护特性的丧失,而年轻个体和实验动物的睑脂为眼睛提供了充分的保护。目前,睑脂生物合成(称为meibogenesis)的分子机制尚未完全了解。为了表征发育和成熟MG的生理变化,我们研究了从新生儿到成年小鼠MG的脂质体和转录组。结果显示,与其各自脂质产物的生物合成正相关的减数分裂的关键基因(例如Elovl 3、Elovl 4、Awat 2和Soat 1等)逐渐增加。还使用单细胞RNA测序分析了年轻和成年小鼠的MG转录组。这些实验揭示了存在多个独特的MG细胞群体(睑板细胞、上皮细胞等),其具有编码睑板发生相关蛋白的基因的特定组合,并鉴定了暂时分类为处于不同分化/成熟阶段的睑板细胞或其祖细胞的细胞簇和亚簇。提出了一个假设,即这些细胞可能产生不同类型的脂质,并对睑板腺脂质组有不同的贡献。
Meibomian glands (MGs) and their holocrine secretion—meibum—play crucial roles in the physiology of the eye, providing protection from environmental factors and desiccation, among other functions. Importantly, aging was implicated in the deterioration of the morphology and functions of MGs, and the quantity and quality of meibum they produce, leading to a loss of its protective properties, while the meibum of young individuals and experimental animals provide ample protection to the eye. Currently, the molecular mechanisms of meibum biosynthesis (termed meibogenesis) are not fully understood. To characterize the physiological changes in developing and maturing MGs, we studied the lipidomes and transcriptomes of mouse MGs ranging from newborns to adults. The results revealed a gradual increase in the critical genes of meibogenesis (such as Elovl3, Elovl4, Awat2, and Soat1, among others) that positively correlated with the biosynthesis of their respective lipid products. The MG transcriptomes of young and adult mice were also analyzed using single-cell RNA sequencing. These experiments revealed the existence of multiple unique populations of MG cells (meibocytes, epithelial cells, and others) with specific combinations of genes that encode meibogenesis-related proteins, and identified clusters and subclusters of cells that were tentatively classified as meibocytes at different stages of differentiation/maturation, or their progenitor cells. A hypothesis was formulated that these cells may produce different types of lipids, and contribute differentially to the Meibomian lipidome.
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