Transcriptional trajectories of human kidney injury progression
作者： Pietro E. Cippà , Bo Sun , Jing Liu , Liang Chen , Maarten Naesens
DOI: 10.1172/JCI.INSIGHT.123151
关键词:
摘要: BACKGROUND. The molecular understanding of the progression from acute to chronic organ injury is limited. Ischemia/reperfusion (IRI) triggered during kidney transplantation can contribute progressive allograft dysfunction. METHODS. Protocol biopsies (n = 163) were obtained 42 allografts at 4 time points after transplantation. RNA sequencing–mediated (RNA-seq–mediated) transcriptional profiling and machine learning computational approaches employed analyze responses IRI identify shared divergent trajectories associated with distinct clinical outcomes. data compared response in a mouse model transition. RESULTS. In first hours reperfusion, all patients exhibited similar program under control immediate-early genes. following months, we identified 2 main leading recovery or sustained fibrosis renal dysfunction. map generated by this approach highlighted early markers disease delineated programs transition injury. characterization process extended relevance our findings beyond transplantation. CONCLUSIONS. integration multiple transcriptomes serial advanced algorithms overcame analytical hurdles related variability between individuals elements humans, which may prove as useful predictors This generally applicable opens way for an unbiased analysis human progression. FUNDING. study was supported California Institute Regenerative Medicine Swiss National Science Foundation.
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