Transcriptomics of mouse hepatocyte maturation and human hepatic reprogramming
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA717728 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14078360_1.fastq.gz | Fastqsanger.gz | |||
| SRR14078360_2.fastq.gz | Fastqsanger.gz | |||
| SRR14078361_1.fastq.gz | Fastqsanger.gz | |||
| SRR14078361_2.fastq.gz | Fastqsanger.gz | |||
| SRR14078362_1.fastq.gz | Fastqsanger.gz |
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Project description:Liver fibrosis is a strong predictor of long-term mortality in patients with non-alcoholic fatty liver disease; yet the mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis are incompletely under-stood. Using a cell type-resolved genomics approach, we show that comprehensive alterations in hepatocyte genomic and transcriptional settings during NASH progression, led to a partial loss of hepatocyte identity. The hepatocyte reprogramming was under tight cooperative control of a net-work of NASH-activated transcription factors (TFs), as exemplified by Elf3 and Glis2. Indeed, Elf3 and Glis2 controlled hepatocyte identity and fibrosis-dependent hepatokine genes targeting disease-associated hepatic stellate cell (HSC) gene programs. Thus, interconnected TF networks not only promoted hepatocyte dysfunction, but also directed the intra-hepatic crosstalk with HSCs necessary for NASH and fibrosis progression implying molecular “hub-centered” targeting strategies to be superior to existing mono-target approaches as currently used in NASH therapy.
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