Dataset Information

Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice.

ABSTRACT: The kidney's inherent complexity has made identifying cell-specific pathways challenging, particularly when temporally associating them with the dynamic pathophysiology of acute kidney injury (AKI). Here, we combine renal cell-specific luciferase reporter mice using a chemoselective luciferin to guide the acquisition of cell-specific transcriptional changes in C57BL/6 background mice. Hydrogen peroxide generation, a common mechanism of tissue damage, was tracked using a peroxy-caged-luciferin to identify optimum time points for immunoprecipitation of labeled ribosomes for RNA-sequencing. Together, these tools revealed a profound impact of AKI on mitochondrial pathways in the collecting duct. In fact, targeting the mitochondria with an antioxidant, ameliorated not only hydrogen peroxide generation, but also significantly reduced oxidative stress and the expression of the AKI biomarker, LCN2. This integrative approach of coupling physiological imaging with transcriptomics and drug testing revealed how the collecting duct responds to AKI and opens new venues for cell-specific predictive monitoring and treatment.

SUBMITTER: Miyazaki T

PROVIDER: S-EPMC6718519 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice.

Miyazaki Tomoaki T Gharib Sina A SA Hsu Yun-Wei A YA Xu Katherine K Khodakivskyi Pavlo P Kobayashi Akio A Paragas Jason J Klose Alexander D AD Francis Kevin P KP Dubikovskaya Elena E Page-McCaw Patrick S PS Barasch Jonathan J Paragas Neal N

Communications biology 20190902

The kidney's inherent complexity has made identifying cell-specific pathways challenging, particularly when temporally associating them with the dynamic pathophysiology of acute kidney injury (AKI). Here, we combine renal cell-specific luciferase reporter mice using a chemoselective luciferin to guide the acquisition of cell-specific transcriptional changes in C57BL/6 background mice. Hydrogen peroxide generation, a common mechanism of tissue damage, was tracked using a peroxy-caged-luciferin to ...[more]

PMID: 31508501

Similar Datasets

Project description:Rationale and objectiveDespite contribution of dyslipidemia to ischemic stroke, plasma lipidomic correlates of stroke in CKD is not studied. This study is aimed to identify plasma lipid alterations associated with stroke.Study designCross sectional.Setting and population214 participants of Clinical Phenotyping and Resource Biobank Core (CPROBE). Clinical data and plasma samples at the time of recruitment were obtained and used to generate lipidomic data by liquid chromatography/mass-spectrometry-based untargeted platform.PredictorsVarious levels of free fatty acids, acylcarnitines and complex lipids.OutcomeStroke.Analytic approachincludes compound by compound comparison of lipids using t-test adjusted by false discovery rate in patients with and without stroke, and application of logistic regression analysis to identify independent lipid predictors of stroke and to estimate the odds associated with their various levels.ResultsOverall, we identified 330 compounds. Enrichment analysis revealed overrepresentation of differentially regulated phosphatidylcholines (PC)s and phosphatidylethanolamines (PE)s were overrepresented in stroke (P<0.001). Abundance of PC38:4, PE36:4, PC34:0, and palmitate were significantly higher, but those of plasmenyl-PE (pPE)38:2, and PE 32:2 was significantly lower in patients with stroke (p≤0.0014). After adjusting, each 1-SD increase in palmitate and PC38:4 was independently associated with 1.84 fold (95% CI: 1.06-3.20, p=0.031) and 1.84 fold (1.11-3.05, p=0.018) higher risk of stroke, respectively. We observed a significant trend toward higher abundance of PCs, PEs, pPEs, and sphingomyelins in stroke (p≤0.046).LimitationsSmall sample size; unclear, if similar changes in the same or opposite direction preceded stroke, as the cross-sectional nature of the observation does not allow determining the effect of time course on lipid alterations.ConclusionDifferential regulation of palmitate, PCs, and PEs in patients with CKD and a history of stroke may represent a previously unrecognized risk factor and might be a target of risk stratification and modification.

Dataset Information

Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice.

Publications

Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets