Babraham Institute, Cambridge, CB22 3AT, UK.
The Francis Crick Institute, London, NW1 1AT, UK.
Sci Rep. 2019 Jul 18;9(1):10410. doi: 10.1038/s41598-019-46966-3.
The intestinal epithelium undergoes constant regeneration driven by intestinal stem cells. How old age affects the transcriptome in this highly dynamic tissue is an important, but poorly explored question. Using transcriptomics on sorted intestinal stem cells and adult enterocytes, we identified candidate genes, which change expression on aging. Further validation of these on intestinal epithelium of multiple middle-aged versus old-aged mice highlighted the consistent up-regulation of the expression of the gene encoding chemokine receptor Ccr2, a mediator of inflammation and several disease processes. We observed also increased expression of Strc, coding for stereocilin, and dramatically decreased expression of Rps4l, coding for a ribosome subunit. Ccr2 and Rps4l are located close to the telomeric regions of chromosome 9 and 6, respectively. As only few genes were differentially expressed and we did not observe significant protein level changes of identified ageing markers, our analysis highlights the overall robustness of murine intestinal epithelium gene expression to old age.
肠道上皮细胞由肠道干细胞驱动,不断进行自我更新。年龄如何影响这个高度动态组织的转录组是一个重要但尚未得到充分探索的问题。我们通过对分选的肠道干细胞和成年肠细胞进行转录组学分析,鉴定了候选基因,这些基因在衰老过程中表达发生变化。进一步在多个中年和老年小鼠的肠道上皮细胞中验证这些基因,突出了趋化因子受体 Ccr2 的表达上调,Ccr2 是炎症和几种疾病过程的介质。我们还观察到编码立体蛋白的 Strc 和编码核糖体亚基的 Rps4l 的表达显著降低。Ccr2 和 Rps4l 分别位于染色体 9 和 6 的端粒区域附近。由于只有少数基因表达存在差异,并且我们没有观察到鉴定出的衰老标志物的蛋白质水平发生显著变化,因此我们的分析强调了小鼠肠道上皮细胞基因表达对衰老的整体稳健性。