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http://hdl.handle.net/2445/173043
Title: | The nuclear receptor ESRRA protects from kidney disease by coupling metabolism and differentiation |
Author: | Dhillon, Poonam Park, Jihwan Hurtado del Pozo, Carmen Li, Lingzhi Doke, Tomohito Huang, Shizheng Zhao, Juanjuan Kang, Hyun Mi Shrestra, Rojesh Balzer, Michael S. Chatterjee, Shatakshee Prado, Patricia Han, Seung Yub Liu, Hongbo Sheng, Xin Dierickx, Pieterjan Batmanov, Kirill Romero, Juan P. Prósper, Felipe Li, Mingyao Pei, Liming Kim, Junhyong Montserrat, Núria Susztak, Katalin |
Keywords: | Malalties del ronyó RNA Kidney diseases RNA |
Issue Date: | 9-Dec-2020 |
Abstract: | Kidney disease is poorly understood because of the organ’s cellular diversity. We used single-cell RNA sequencing not only in resolving differences in injured kidney tissue cellular composition but also in cell-type-specific gene expression in mouse models of kidney disease. This analysis highlighted major changes in cellular diversity in kidney disease, which markedly impacted whole-kidney transcriptomics outputs. Cell-type-specific differential expression analysis identified proximal tubule (PT) cells as the key vulnerable cell type. Through unbiased cell trajectory analyses, we show that PT cell differentiation is altered in kidney disease. Metabolism (fatty acid oxidation and oxidative phosphorylation) in PT cells showed the strongest and most reproducible association with PT cell differentiation and disease. Coupling of cell differentiation and the metabolism was established by nuclear receptors (estrogen-related receptor alpha [ESRRA] and peroxisomal proliferation-activated receptor alpha [PPARA]) that directly control metabolic and PT-cell-specific gene expression in mice and patient samples while protecting from kidney disease in the mouse model. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.cmet.2020.11.011 |
It is part of: | Cell Metabolism, 2020, vol. 33, num. 2, p. 379-394 |
URI: | http://hdl.handle.net/2445/173043 |
Related resource: | https://doi.org/10.1016/j.cmet.2020.11.011 |
Appears in Collections: | Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) Publicacions de projectes de recerca finançats per la UE |
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L20_2020_Cell Metabolism_X_X_OA.pdf | 11.96 MB | Adobe PDF | View/Open |
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