Bulk RNA-seq of mice covering the whole lifespan (2 days to 904 days) from four tissues

Gene expression changes during ageing were shown to oppose developmental trajectories; a reversal pattern previously linked to cellular identity loss. Generating cortex, lung, liver and muscle tissue transcriptomes of 16 mice of different ages, covering development and ageing periods, we found that expression reversals were widespread but tissue-specific. Consistent with this result, we observed an inter-tissue divergence during development and convergence during ageing (DiCo), further confirmed in independent mouse and human datasets. The genes displaying DiCo pattern were enriched among tissue-specific genes that tended to lose developmental expression levels during ageing. Finally, analysing publicly available single-cell transcriptome data, we studied the contribution of cellular composition and cell-autonomous changes to the convergence in ageing. Our results, for the first time, suggest inter-tissue convergence during ageing is widespread and associated with the loss of specialisation at the tissue and possibly also at the cellular level. Age-series mRNA expression profiles from 4 tissues (cerebral cortex, lung, liver, skeletal muscle) of 16 mice, covering postnatal development (2 days - 61 days) and ageing (93 days - 904 days) periods.已有研究显示，衰老过程中的基因表达变化与发育轨迹方向相反；此前这种逆转模式曾被证实与细胞身份丧失存在关联。 我们对覆盖发育与衰老阶段的16只不同月龄小鼠的大脑皮层、肺、肝脏及肌肉组织开展转录组（transcriptome）测序，结果发现基因表达逆转现象广泛存在，但具有组织特异性。 与该结果一致的是，我们观察到发育阶段的组织间表达分化与衰老阶段的组织间表达趋同（DiCo）现象，该结果在独立的小鼠与人类数据集上得到了进一步验证。 呈现DiCo模式的基因在那些在衰老过程中倾向于丢失发育阶段表达水平的组织特异性基因中显著富集。 最后，通过分析公开可用的单细胞转录组（single-cell transcriptome）数据，我们探究了细胞组成与细胞自主变化对衰老阶段趋同现象的贡献。 本研究首次表明，衰老过程中的组织间趋同现象广泛存在，且与组织层面乃至可能的细胞层面的特化功能丧失相关。 本数据集包含16只小鼠的4种组织（大脑皮层、肺、肝脏、骨骼肌）的年龄序列mRNA表达谱，覆盖出生后发育阶段（2日龄至61日龄）与衰老阶段（93日龄至904日龄）。