Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
The GOFARR Laboratory, The Saban Research Institute, Division of Urology, Children's Hospital Los Angeles, Los Angeles, California, USA.
JCI Insight. 2024 Mar 22;9(6):e165515. doi: 10.1172/jci.insight.165515.
Here, we used digital spatial profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways with progressively decreased expression in response to increasing pathology scores, including signal recognition particle-dependent cotranslational protein targeting to membrane and selenocysteine synthesis pathways. We also identified a distinct signature of upregulated and downregulated genes common to all the diseases investigated when compared with nondiseased tissue from nephrectomies. These analyses using DSP at the single-glomerulus level could help to increase insight into the pathophysiology of kidney disease and possibly the identification of biomarkers of disease progression in glomerulopathies.
在这里，我们使用数字空间分析（DSP）来描述肾小球转录组特征，这些特征可能有助于阐明 Alport 综合征、局灶节段性肾小球硬化症和膜性肾病中导致进行性肾脏疾病的复杂分子机制。我们的结果显示，病变肾小球之间存在显著的转录异质性，并且这种分析表明，组织学上相似的肾小球表现出不同的转录谱。我们使用肾小球病理评分来建立一个进展轴，确定了随着病理评分增加而表达逐渐降低的分子途径，包括信号识别颗粒依赖性共翻译蛋白靶向到膜和硒代半胱氨酸合成途径。我们还发现了一个与所有研究疾病相比，上调和下调基因的独特特征，与肾切除术的非病变组织相比。这些使用 DSP 在单个肾小球水平上的分析可以帮助增加对肾脏疾病病理生理学的深入了解，并可能有助于鉴定肾小球病中疾病进展的生物标志物。
