GEO series

Hepatocyte CCAAT/enhancer-binding protein alpha restricts liver fibrosis by inhibiting secreted phosphoprotein 1 expression (II)

GSE214615 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/03/08 Platform GPL19057

At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 12 samples: 3 × PMH, WT vs 3 × PMH, KO vs 3 × PMH, GFP vs 3 × PMH, OEGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Hepatocyte-specific CCAAT/enhancer binding protein α restricts liver fibrosis progressionThe Journal of clinical investigation · 2024

Summary (written by the submitters)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Persistent NAFLD can progress to nonalcoholic steatohepatitis (NASH) with inflammation and fibrosis, which predisposes patients to cirrhosis and hepatocellular carcinoma. CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor that modulates glycolipid homeostasis, cell differentiation and tumor progression.

Read the full summary ↓

MTL-CEBPA, a first-in-human small activating RNA therapeutic, has been used to overexpress CEBPA and treat hepatocellular carcinoma by targeting myeloid cells in clinical trials. However, whether and how hepatocyte-specific CEBPA modulates NASH are unknown. Here we found that CEBPA expression was inhibited in the livers of high-fat, high-cholesterol, and high-fructose diet (HFCFD)-fed mice, NASH patients and palmitic/oleic acid-treated primary hepatocytes. Liver-specific Cebpa knockout mice (Cebpa-dLiv) and liver-specific tamoxifen-inducible ERT2-Cre mice (Cebpa-dLiv-ERT2) were then generated. Both Cebpa-dLiv and Cebpa-dLiv-ERT2 mice (treated with tamoxifen) developed enhanced NASH and fibrosis compared to control mice. Global transcriptome analyses demonstrated hepatic secreted phosphoprotein 1 (Spp1) encoding the fibrosis-promoting factor SPP1, was markedly induced by hepatocyte CEBPA knockout in HFCFD-fed mice. Consistently, hepatic SPP1 was upregulated by NASH and negatively correlated with CEBPA expression in humans. Hepatocyte loss of CEBPA enhanced hepatic SPP1 expression and serum SPP1 levels both at the early and late stage of NASH in mice. CEBPA-knockout primary hepatocytes released more SPP1 to the culture medium than wild-type mouse hepatocytes, resulting in enhanced fibrogenesis of hepatic stellate cells, a phenotype that was rescued by the Spp1 shRNA. Hepatocyte-directed AAV8-deliverey of Spp1 shRNA rescued the fibrosis in HFCFD-fed Cebpa-dLiv mice. Mechanistically, CEBPA overexpression reduced, while CEBPA knockout enhanced, SPP1 expression in primary hepatocytes in vitro. The Spp1 promoter had functional CEBPA response elements, while CEBPA modulated histone acetylation to restrict SPP1 expression in a novel feedback loop. Furthermore, overexpression of CEBPA in hepatocytes with AAV8-TBG-CEBPA, inhibited hepatic SPP1 expression and reduced fibrosis in HFCFD-fed wild-type mice. This study demonstrates a novel hepatocyte CEBPA-SPP1 axis involved in modulating NASH fibrosis that supports hepatocyte CEBPA as an anti-NASH target.

Published in

Hepatocyte-specific CCAAT/enhancer binding protein α restricts liver fibrosis progression

Yan T, Yan N, Xia Y et al. · The Journal of clinical investigation 2024 · PMID 38557493 · doi:10.1172/JCI166731

This dataset

Open GSE214615 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE214615_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA886403 and SRA study SRP400659. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38557493) ↗

Study design

3 × PMH, WT vs 3 × PMH, KO vs 3 × PMH, GFP vs 3 × PMH, OE

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM6613102 PMH, WT1 PMH, WT
GSM6613103 PMH, WT2 PMH, WT
GSM6613104 PMH, WT3 PMH, WT
GSM6613105 PMH, KO1 PMH, KO
GSM6613106 PMH, KO2 PMH, KO
GSM6613107 PMH, KO3 PMH, KO
GSM6613108 PMH, GFP1 PMH, GFP
GSM6613109 PMH, GFP2 PMH, GFP
GSM6613110 PMH, GFP3 PMH, GFP
GSM6613111 PMH, OE1 PMH, OE
GSM6613112 PMH, OE2 PMH, OE
GSM6613113 PMH, OE3 PMH, OE

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.