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Series GSE129933 Query DataSets for GSE129933
Status Public on Apr 18, 2019
Title Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded.
Overall design Single-cell RNA-seq analysis of human liver lymphatic endothelial cells.
Contributor(s) Tamburini BA, Finlon JM, Gillen AE, Kriss MS, Riemondy KA, Fu R, Schuyler R, Hesselberth JR, Rosen HR, Burchill MA
Citation(s) 31156626
Submission date Apr 17, 2019
Last update date Jun 21, 2019
Contact name Matthew Alan Burchill
Phone 303-724-7228
Organization name University of Colorado - Anschutz Medical Campus
Department Department of Medicine
Street address 12700 E. 19th Avenue, P15, RM10119
City Aurora
State/province Colorado
ZIP/Postal code 80045
Country USA
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (4)
GSM3728304 LEC-enriched hepatic non-parenchymal cells (Non-Diseased, rep 1)
GSM3728305 LEC-enriched hepatic non-parenchymal cells (Non-Diseased, rep 2)
GSM3728306 LEC-enriched hepatic non-parenchymal cells (NASH)
BioProject PRJNA533227
SRA SRP192823

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE129933_cell_metadata.tsv.gz 20.3 Kb (ftp)(http) TSV
GSE129933_count_matrix.tsv.gz 722.7 Kb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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