Integrating Metabolomics and Transcriptomics to Characterize Differential Functional Capabilities of Kidney Proximal Tubule Cell Subtypes

Abstract

The coupling between energy metabolism and transport processes is a key feature that defines the functional capability of proximal tubule cells. Recent studies using metabolomics and transcriptomics provide insights into the relationships between changes in single-cell transcriptomic profiles and energy metabolism during kidney development and in disease states. In this review, we describe insights from these studies and how mapping of metabolites to functional pathways within cells enables these insights. We also describe our analyses of fatty acid metabolism pathways from single-cell transcriptomic data obtained by the Kidney Precision Medicine Project, which indicate that proximal tubule cell subtypes can be divided into two major groups with high and low levels of mRNAs for fatty acid (beta) oxidation enzymes. On average, patients with CKD have higher levels of cells with low fatty acid oxidation capability. These cells also have lower levels of sodium transporters. Within each group of proximal tubule cell subtypes there is considerable variability between individual patients. Integrating these data with metabolomics analyses can provide insights into how the differential metabolic capabilities of proximal tubule cells are related to disease features in individual patients. Identifying such relationships can lead to development of precision medicine approaches in nephrology.

Keywords: Heterogeneity of metabolic functions; integrating transcriptomics and metabolomics; proximal tubule cell subtypes; spatial metabolomics.