| Literature DB >> 33301705 |
Poonam Dhillon1, Jihwan Park2, Carmen Hurtado Del Pozo3, Lingzhi Li1, Tomohito Doke1, Shizheng Huang1, Juanjuan Zhao4, Hyun Mi Kang5, Rojesh Shrestra1, Michael S Balzer1, Shatakshee Chatterjee1, Patricia Prado3, Seung Yub Han6, Hongbo Liu1, Xin Sheng1, Pieterjan Dierickx7, Kirill Batmanov1, Juan P Romero8, Felipe Prósper8, Mingyao Li9, Liming Pei10, Junhyong Kim6, Nuria Montserrat11, Katalin Susztak12.
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.Entities:
Keywords: ESRRA; PPARA; chronic kidney disease; fatty-acid oxidation; fibrosis; kidney; organoids; proximal tubule cells; single-cell ATAC sequencing; single-cell RNA sequencing
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Year: 2020 PMID： 33301705 PMCID： PMC9259369 DOI： 10.1016/j.cmet.2020.11.011
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 31.373