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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
Kidney diseases
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:
It is part of: Cell Metabolism, 2020, vol. 33, num. 2, p. 379-394
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Appears in Collections:Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

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