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| Status |
Public on Feb 05, 2024 |
| Title |
Kupffer cells dictate hepatic responses to the atherogenic dyslipidemic insult (scRNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Apolipoprotein-B (APOB)-containing lipoproteins cause atherosclerosis. Whether the vasculature is initially responding site, or if atherogenic-dyslipidemia affects other organs simultaneously, is unknown. Here we show that the liver responds to a dyslipidemic insult based on inducible models of familial hypercholesterolemia and APOB tracing. An acute transition to atherogenic APOB-lipoprotein levels resulted in uptake by Kupffer cells and rapid accumulation of triglycerides and cholesterol in the liver. Bulk and single-cell RNA-seq revealed an Kupffer cell-specific transcriptional program that was not activated by a high-fat diet alone, or detected in standard liver function or pathological assays, even in the presence of fulminant atherosclerosis. Depletion of Kupffer cells altered the dynamic of plasma and liver lipid concentrations, indicating that these liver macrophages help restrain and buffer atherogenic lipoproteins, whilst simultaneously secreting atherosclerosis-modulating factors into plasma. Our results place Kupffer cells as key sentinels in organizing systemic responses to lipoproteins at the initiation of atherosclerosis.
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| Overall design |
Liver sample from D374YmCherry-APOB mice. Mice were maintained on a chow diet for 10 days after tamoxifen.
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| Contributor(s) |
Malin S |
| Citation missing |
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| Submission date |
Feb 02, 2024 |
| Last update date |
Feb 06, 2024 |
| Contact name |
Stephen Malin |
| E-mail(s) |
stephen.malin@ki.se
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| Organization name |
Karolinska Institutet
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| Street address |
Bioclinicum J8:20, Visionsgatan 4
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| City |
Stockholm |
| ZIP/Postal code |
17164 |
| Country |
Sweden |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA1072727 |
