Helmholtz Gemeinschaft


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

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplementary Material)

Item Type:Article
Title:Metabolic characterization of directly reprogrammed renal tubular epithelial cells (iRECs)
Creators Name:Lagies, S. and Pichler, R. and Kaminski, M.M. and Schlimpert, M. and Walz, G. and Lienkamp, S.S. and Kammerer, B.
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 fibroblasts into renal tubular epithelial cells strongly influences the metabolome of engineered cells, suggesting that metabolic profiling may aid in establishing iRECs as in vitro models for nephrotoxicity testing in the future.
Keywords:Cell Differentiation, Cellular Reprogramming, Cluster Analysis, Epithelial Cells, Fibroblasts, Gas Chromatography-Mass Spectrometry, Inbred C57BL Mice, Kidney Tubules, Metabolome, Metabolomics, Transcription Factors, Animals, Mice
Source:Scientific Reports
Publisher:Nature Publishing Group
Page Range:3878
Date:1 March 2018
Official Publication:https://doi.org/10.1038/s41598-018-22073-7
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library