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| Status |
Public on Dec 02, 2024 |
| Title |
Visium spatial transcriptomics and proteomics identifies novel hepatic cell populations and transcriptomic signatures of alcohol-associated hepatitis |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
Background: Alcohol-associated hepatitis (AH) is the clinical manifestation of alcohol-associated liver disease (ALD). AH is a complex disease encompassing the dysregulation of many cells and cell subpopulations. This study used a hepatic spatial transcriptomic and proteomic approach (10X Genomics Visium) to identify hepatic cell populations and their associated transcriptomic and proteomic alterations in human AH. Methods: Formalin fixed parraffin embedded liver tissue from AH patients (n=2) and non-ALD controls (donors) (n=2) were used for Visium spatial transcriptomic and proteomic analysis. Results: AH cell clusters and cell markers were drastically different in regard to tissue pattern and number of cell type as compared to non-ALD controls. Cholangiocytes, endothelial cells, macrophages, and stellate cells were more profuse in AH relative to non-ALD controls. Transcriptionally, proliferating cell nuclear antigen positive (PCNA+) hepatocytes in AH more closely resembled cholangiocytes suggesting they were non-functional hepatocytes derived from cholangiocytes. Further, mitochondria protein coding genes were reduced in AH vs non-ALD control hepatocytes, suggesting reduced functionality and loss of regenerative mechanisms. Macrophages in AH exhibited elevated gene expression involved in exosomes as compared to non-ALD controls. The most upregulated macrophage genes observed in AH were those involved in exosome trafficking and cellular migration. Gene and protein signatures of disease associated hepatocytes (ANXA2+/CXCL1+/CEACAM8+) were elevated in AH and could visually identify a pre-malignant lesion. Conclusions: This study identified global cell type alterations in AH and distinct transcriptomic changes between AH and non-ALD controls. These findings characterizes cellular plasticity and profuse transcriptomic and proteomic changes that are apparent in AH and contributes to the identification of novel therapeutics.
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| Overall design |
FFPE liver sections from non-ALD controls (n=2) and alcohol-associated hepatitis patients (n=3) were used for Visium spatial transcriptomic and proteomic analysis.
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| Contributor(s) |
Gripshover TC, Treves RS, Rouchka EC, Chariker JH, Zheng S, Hudson E, Smith ML, Singal AK, McClain CJ, Hardesty JE |
| Citation(s) |
39592394 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P20 GM103436 |
IDeA Networks of Biomedical Research Excellence in Kentucky |
UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION |
Martha E Bickford |
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| Submission date |
Oct 02, 2024 |
| Last update date |
Dec 02, 2024 |
| Contact name |
Eric Christian Rouchka |
| E-mail(s) |
eric.rouchka@louisville.edu
|
| Organization name |
University of Louisville
|
| Department |
Biochemistry and Molecular Genetics
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| Lab |
KY INBRE Bioinformatics Core
|
| Street address |
522 East Gray Street
|
| City |
Louisville |
| State/province |
Kentucky |
| ZIP/Postal code |
40292 |
| Country |
USA |
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| Platforms (1) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1168162 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE278662_N123_aligned_fiducials.jpg.gz |
2.2 Mb |
(ftp)(http) |
JPG |
| GSE278662_N123_aligned_tissue_image.jpg.gz |
897.8 Kb |
(ftp)(http) |
JPG |
| GSE278662_N123_barcodes.tsv.gz |
27.2 Kb |
(ftp)(http) |
TSV |
| GSE278662_N123_cytassist_image.tiff.gz |
20.0 Mb |
(ftp)(http) |
TIFF |
| GSE278662_N123_detected_tissue_image.jpg.gz |
1.0 Mb |
(ftp)(http) |
JPG |
| GSE278662_N123_features.tsv.gz |
291.3 Kb |
(ftp)(http) |
TSV |
| GSE278662_N123_matrix.mtx.gz |
43.6 Mb |
(ftp)(http) |
MTX |
| GSE278662_N123_raw_feature_bc_matrix.h5.gz |
16.7 Mb |
(ftp)(http) |
H5 |
| GSE278662_N123_scalefactors_json.json.gz |
174 b |
(ftp)(http) |
JSON |
| GSE278662_N123_spatial_enrichment.csv.gz |
756.2 Kb |
(ftp)(http) |
CSV |
| GSE278662_N123_tissue_hires_image.png.gz |
4.0 Mb |
(ftp)(http) |
PNG |
| GSE278662_N123_tissue_lowres_image.png.gz |
352.8 Kb |
(ftp)(http) |
PNG |
| GSE278662_N123_tissue_positions.csv.gz |
58.3 Kb |
(ftp)(http) |
CSV |
| GSE278662_N126_aligned_fiducials.jpg.gz |
2.6 Mb |
(ftp)(http) |
JPG |
| GSE278662_N126_aligned_tissue_image.jpg.gz |
871.4 Kb |
(ftp)(http) |
JPG |
| GSE278662_N126_barcodes.tsv.gz |
27.2 Kb |
(ftp)(http) |
TSV |
| GSE278662_N126_cytassist_image.tiff.gz |
21.5 Mb |
(ftp)(http) |
TIFF |
| GSE278662_N126_detected_tissue_image.jpg.gz |
1.0 Mb |
(ftp)(http) |
JPG |
| GSE278662_N126_features.tsv.gz |
291.3 Kb |
(ftp)(http) |
TSV |
| GSE278662_N126_matrix.mtx.gz |
41.2 Mb |
(ftp)(http) |
MTX |
| GSE278662_N126_raw_feature_bc_matrix.h5.gz |
16.1 Mb |
(ftp)(http) |
H5 |
| GSE278662_N126_scalefactors_json.json.gz |
173 b |
(ftp)(http) |
JSON |
| GSE278662_N126_spatial_enrichment.csv.gz |
785.4 Kb |
(ftp)(http) |
CSV |
| GSE278662_N126_tissue_hires_image.png.gz |
5.5 Mb |
(ftp)(http) |
PNG |
| GSE278662_N126_tissue_lowres_image.png.gz |
496.9 Kb |
(ftp)(http) |
PNG |
| GSE278662_N126_tissue_positions.csv.gz |
66.2 Kb |
(ftp)(http) |
CSV |
| GSE278662_Sah73_aligned_fiducials.jpg.gz |
2.5 Mb |
(ftp)(http) |
JPG |
| GSE278662_Sah73_aligned_tissue_image.jpg.gz |
976.4 Kb |
(ftp)(http) |
JPG |
| GSE278662_Sah73_barcodes.tsv.gz |
27.2 Kb |
(ftp)(http) |
TSV |
| GSE278662_Sah73_cytassist_image.tiff.gz |
20.9 Mb |
(ftp)(http) |
TIFF |
| GSE278662_Sah73_detected_tissue_image.jpg.gz |
1.0 Mb |
(ftp)(http) |
JPG |
| GSE278662_Sah73_features.tsv.gz |
291.3 Kb |
(ftp)(http) |
TSV |
| GSE278662_Sah73_matrix.mtx.gz |
17.4 Mb |
(ftp)(http) |
MTX |
| GSE278662_Sah73_raw_feature_bc_matrix.h5.gz |
7.3 Mb |
(ftp)(http) |
H5 |
| GSE278662_Sah73_scalefactors_json.json.gz |
175 b |
(ftp)(http) |
JSON |
| GSE278662_Sah73_spatial_enrichment.csv.gz |
794.1 Kb |
(ftp)(http) |
CSV |
| GSE278662_Sah73_tissue_hires_image.png.gz |
3.9 Mb |
(ftp)(http) |
PNG |
| GSE278662_Sah73_tissue_lowres_image.png.gz |
333.6 Kb |
(ftp)(http) |
PNG |
| GSE278662_Sah73_tissue_positions.csv.gz |
66.1 Kb |
(ftp)(http) |
CSV |
| GSE278662_Sah80_aligned_fiducials.jpg.gz |
2.2 Mb |
(ftp)(http) |
JPG |
| GSE278662_Sah80_aligned_tissue_image.jpg.gz |
1.1 Mb |
(ftp)(http) |
JPG |
| GSE278662_Sah80_barcodes.tsv.gz |
27.2 Kb |
(ftp)(http) |
TSV |
| GSE278662_Sah80_cytassist_image.tiff.gz |
20.1 Mb |
(ftp)(http) |
TIFF |
| GSE278662_Sah80_detected_tissue_image.jpg.gz |
1.1 Mb |
(ftp)(http) |
JPG |
| GSE278662_Sah80_features.tsv.gz |
291.3 Kb |
(ftp)(http) |
TSV |
| GSE278662_Sah80_matrix.mtx.gz |
36.1 Mb |
(ftp)(http) |
MTX |
| GSE278662_Sah80_raw_feature_bc_matrix.h5.gz |
14.1 Mb |
(ftp)(http) |
H5 |
| GSE278662_Sah80_scalefactors_json.json.gz |
176 b |
(ftp)(http) |
JSON |
| GSE278662_Sah80_spatial_enrichment.csv.gz |
768.0 Kb |
(ftp)(http) |
CSV |
| GSE278662_Sah80_tissue_hires_image.png.gz |
5.6 Mb |
(ftp)(http) |
PNG |
| GSE278662_Sah80_tissue_lowres_image.png.gz |
519.5 Kb |
(ftp)(http) |
PNG |
| GSE278662_Sah80_tissue_positions.csv.gz |
64.5 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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