Metabolic characterization of directly reprogrammed renal tubular epithelial cells (iRECs)

Scientific Reports
Simon LagiesBernd Kammerer

Abstract

Fibroblasts can be directly reprogrammed to induced renal tubular epithelial cells (iRECs) using four transcription factors. These engineered cells may be used for disease modeling, cell replacement therapy or drug and toxicity testing. Direct reprogramming induces drastic changes in the transcriptional landscape, protein expression, morphological and functional properties of cells. However, how the metabolome is changed by reprogramming and to what degree it resembles the target cell type remains unknown. Using untargeted gas chromatography-mass spectrometry (GC-MS) and targeted liquid chromatography-MS, we characterized the metabolome of mouse embryonic fibroblasts (MEFs), iRECs, mIMCD-3 cells, and whole kidneys. Metabolic fingerprinting can distinguish each cell type reliably, revealing iRECs are most similar to mIMCD-3 cells and clearly separate from MEFs used for reprogramming. Treatment with the cytotoxic drug cisplatin induced typical changes in the metabolic profile of iRECs commonly occurring in acute renal injury. Interestingly, metabolites in the medium of iRECs, but not of mIMCD-3 cells or fibroblast could distinguish treated and non-treated cells by cluster analysis. In conclusion, direct reprogramming of fibroblas...Continue Reading

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Citations

May 2, 2019·Metabolomics : Official Journal of the Metabolomic Society·Manuel SchlimpertBernd Kammerer
Sep 27, 2019·Cells·Simon LagiesBernd Kammerer
Apr 14, 2020·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Kenichi Horisawa, Atsushi Suzuki
Sep 18, 2020·Antioxidants·Adrienne Bushau-SprinkleEleanor Lederer
Nov 7, 2019·Metabolites·Daqiang PanBernd Kammerer
May 25, 2021·Metabolomics : Official Journal of the Metabolomic Society·Michel KatherArne Liebau

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Methods Mentioned

BETA
metabolome profiling
PCA
metabolomic profiling

Software Mentioned

MRM
Quantitative Analysis software
metaboanalyst
spectconnect
- Optimizer

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