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Spatial reconstruction of the early hepatic transcriptomic landscape after an acetaminophen overdose using single-cell RNA sequencing

Citation

Umbaugh, David; Ramachandran, Anup; Jaeschke, Hartmut (2022), Spatial reconstruction of the early hepatic transcriptomic landscape after an acetaminophen overdose using single-cell RNA sequencing, Dryad, Dataset, https://doi.org/10.5061/dryad.t76hdr806

Abstract

We leveraged single-cell RNA sequencing to understand the early molecular events that define the hepatocyte response to acetaminophen exposure at a subpopulation level. We spatially assigned hepatocytes along the portol-central vein axis by using established landmark genes. By spatially assigning the hepatocytes were were able to account for innate differences in gene expression that existed along this gradient. The excel files herein provide the full list of differentially expressed genes between key subpopulations of interest. Additionally, we classified genes as either pericentral zonated, periportal zonated, or non-zonated, the full list of genes and their spatial assignments are included in the appropriate excel file. 

Methods

This is processed single-cell data from Genomics single cell 3' end expression 10x chromium. 

Additional File 1

Description: Table indicating number of hepatocytes, low confidence hepatocytes, endothelial and Kupffer cells identified within either the control or APAP dataset.

Additional File 2

Description: List of all sampled genes from control hepatocytes, ordered based on mean square error, assigned either as perivenous (PV, e.g. pericentral), periportal (PP) or no zonation.

Additional File 3

Description: List of all sampled genes from APAP hepatocytes, ordered based on mean square error, assigned either as perivenous (PV, e.g. pericentral), periportal (PP) or no zonation.

Additional File 4

Description: Pearson correlations comparing zonation profiles of landmark pericentral or periportal genes.

Additional File 5

Description: Differential expression using Wilcoxon rank sum test in Seurat comparing all APAP hepatocytes to all control hepatocytes.

Additional File 6

Description: Differential expression using Wilcoxon rank sum test in Seurat comparing layer 1 APAP hepatocytes vs layer 1 control hepatocytes.

Additional File 7

Description: Differential expression using Wilcoxon rank sum test in Seurat comparing layer 9 APAP hepatocytes vs layer 9 control hepatocytes.

Additional File 8

Description: Using the AverageExpression () function in Seurat giving gene expression for an ‘average’ cell among the 18 identity classes (e.g. layer 1 APAP, layer 1 control, layer 2 APAP, layer 2 control etc.)

Additional File 9

Description: Differential expression using Wilcoxon rank sum test in Seurat comparing the pericentral clusters that were predominately APAP hepatocytes.

Additional File 10

Description: Differential expression using Wilcoxon rank sum test in Seurat comparing the Glul+/StressHigh subclusters.

Additional File 11

Description: List of all sampled genes from human hepatocytes (GSE124395), ordered based on mean square error, assigned either as perivenous (PV, e.g. pericentral), periportal (PP) or no zonation.

Additional File 12

Description: Count matrix of single-cell RNA seq data, column names are treatment condition, row names are genes.

Funding

National Institute of Diabetes and Digestive

National Institute of General Medicine

NIH, Award: U54 HD 090216

University of Kansas Medical Center

Kidney Diseases, Award: R01 NIDDK 102142,R01 NIDDK 125465

Liver Disease COBRE, Award: P20 GM103549,P30 GM118247

Kansas Intellectual and Developmental Disabilities Research Center

Molecular Regulation of Cell Development and Differentiation, Award: P30 GM122731-03

Frontiers CTSA, Award: UL1TR002366