Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Comput Biol. 2022 Sep;29(9):1031-1044. doi: 10.1089/cmb.2021.0349. Epub 2022 Jul 8.
Various cell types can be derived from stem cells. However, these cells are immature and do not match their adult counterparts in functional capabilities, limiting their use in disease modeling and cell therapies. Thus, it is crucial to understand the mechanisms of maturation in vivo. However, it is unknown if there are genes and pathways conserved across organs during maturation. To address this, we performed a time-series analysis of the transcriptome of the mouse heart, brain, liver, and kidney and analyzed their trajectories over time. In addition, gene regulatory networks were reconstructed to determine overlapping expression patterns. Based on these, we identified commonly upregulated and downregulated pathways across all four organs. Key upstream regulators were also predicted based on the temporal expression of downstream genes. These findings suggest the presence of universal regulators during organ maturation, which may help us develop a general strategy to mature stem cell-derived cells in vitro.
各种细胞类型可以由干细胞衍生而来。然而，这些细胞不成熟，在功能能力上与成年细胞不匹配，限制了它们在疾病建模和细胞治疗中的应用。因此，了解体内成熟的机制至关重要。然而，目前尚不清楚在成熟过程中是否存在器官间保守的基因和途径。为了解决这个问题，我们对小鼠心脏、大脑、肝脏和肾脏的转录组进行了时间序列分析，并分析了它们随时间的轨迹。此外，还重建了基因调控网络以确定重叠的表达模式。在此基础上，我们确定了所有四个器官中共同上调和下调的途径。还根据下游基因的时间表达预测了关键的上游调节剂。这些发现表明在器官成熟过程中存在通用调节剂，这可能有助于我们开发一种通用策略，使体外干细胞衍生的细胞成熟。
