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

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Tytuł:: Metabolic characterization of directly reprogrammed renal tubular epithelial cells (iRECs).
Autorzy:: Lagies S; Center for Biosystems Analysis (ZBSA), Albert-Ludwigs-University Freiburg, Habsburgerstr. 49, 79104, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Albertstr. 19a, 79104, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, 79104, Freiburg, Germany.
Pichler R; Department of Medicine, Renal Division, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
Kaminski MM; Department of Medicine, Renal Division, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
Schlimpert M; Center for Biosystems Analysis (ZBSA), Albert-Ludwigs-University Freiburg, Habsburgerstr. 49, 79104, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Albertstr. 19a, 79104, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, 79104, Freiburg, Germany.
Walz G; Department of Medicine, Renal Division, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.; BIOSS Centre of Biological Signalling Studies, University of Freiburg, Schänzlestr. 18, 79104, Freiburg, Germany.
Lienkamp SS; Department of Medicine, Renal Division, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. .; BIOSS Centre of Biological Signalling Studies, University of Freiburg, Schänzlestr. 18, 79104, Freiburg, Germany. .
Kammerer B; Center for Biosystems Analysis (ZBSA), Albert-Ludwigs-University Freiburg, Habsburgerstr. 49, 79104, Freiburg, Germany. .; BIOSS Centre of Biological Signalling Studies, University of Freiburg, Schänzlestr. 18, 79104, Freiburg, Germany. .
Źródło:: Scientific reports [Sci Rep] 2018 Mar 01; Vol. 8 (1), pp. 3878. Date of Electronic Publication: 2018 Mar 01.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:: Epithelial Cells/*metabolism
Kidney Tubules/*metabolism
Animals ; Cell Differentiation/physiology ; Cellular Reprogramming/physiology ; Cluster Analysis ; Fibroblasts/metabolism ; Gas Chromatography-Mass Spectrometry/methods ; Metabolome/genetics ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Transcription Factors/metabolism
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Substance Nomenclature:: 0 (Transcription Factors)
Entry Date(s):: Date Created: 20180303 Date Completed: 20191029 Latest Revision: 20240313
Update Code:: 20240313
PubMed Central ID:: PMC5832874
DOI:: 10.1038/s41598-018-22073-7
PMID:: 29497074
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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.

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