Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; Schepens Eye Research Institute of Massachusetts Eye and Ear, And Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Schepens Eye Research Institute of Massachusetts Eye and Ear, And Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Exp Eye Res. 2021 Apr;205:108452. doi: 10.1016/j.exer.2021.108452. Epub 2021 Jan 22.
We recently discovered that by changing environmental signals, differentiated immortalized human meibomian gland epithelial cells (IHMGECs) de-differentiate into proliferating cells. We also discovered that following exposure to appropriate stimuli, these proliferative cells re-differentiate into differentiated IHMGECs. We hypothesize that this plasticity of differentiated and proliferative IHMGECs is paralleled by very significant alterations in cellular gene expression. To begin to test this hypothesis, we compared the gene expression patterns of IHMGECs during differentiation and proliferation. IHMGECs were cultured for four days in either differentiating or proliferating media. After four days of culture, cells were processed for the analysis of gene expression by using Illumina BeadChips and bioinformatic software. Our study identified significant differences in the expression of more than 9200 genes in differentiated and proliferative IHMGECs. Differentiation was associated with significant increases in the expression of specific genes (e.g. S100 calcium binding protein P; 7,194,386-fold upregulation) and numerous ontologies (e.g. 83 biological process [bp] ontologies with ≥100 genes were upregulated), such as those related to development, transport and lysosomes. Proliferation also led to a significant rise in specific gene expressions (e.g. cathelicidin antimicrobial peptide; 859,100-fold upregulation) and many ontologies (115 biological process [bp] ontologies with ≥100 genes were upregulated), with most of the highly significant ontologies related to cell cycle (z scores > 13.9). Our findings demonstrate that gene expression in differentiated and proliferative IHMGECs is extremely different. These results may have significant implications for the regeneration of HMGECs and the reversal of MG dropout in MG dysfunction.
我们最近发现，通过改变环境信号，分化的永生人类睑板腺上皮细胞（IHMGECs）去分化为增殖细胞。我们还发现，在暴露于适当的刺激后，这些增殖细胞重新分化为分化的 IHMGECs。我们假设，这种分化和增殖的 IHMGECs 的可塑性与细胞基因表达的显著变化相平行。为了开始验证这一假设，我们比较了 IHMGECs 在分化和增殖过程中的基因表达模式。将 IHMGECs 在分化或增殖培养基中培养四天。培养四天后，使用 Illumina BeadChips 和生物信息学软件处理细胞以进行基因表达分析。我们的研究在分化和增殖的 IHMGECs 中发现了超过 9200 个基因表达的显著差异。分化与特定基因表达的显著增加相关（例如 S100 钙结合蛋白 P；上调 7,194,386 倍）和许多本体论（例如，上调了 83 个生物学过程 [bp] 本体论，≥100 个基因上调），例如与发育、运输和溶酶体相关的本体论。增殖也导致特定基因表达的显著上升（例如，抗菌肽 cathelicidin；上调 859,100 倍）和许多本体论（上调了 115 个生物学过程 [bp] 本体论，≥100 个基因上调），其中大多数高度显著的本体论与细胞周期有关（z 分数 > 13.9）。我们的研究结果表明，分化和增殖的 IHMGECs 中的基因表达差异非常大。这些结果可能对 HMGECs 的再生和 MG 功能障碍中 MG 缺失的逆转具有重要意义。
