ArticleMolecular systems biology2020
Endoplasmic reticulum stress actively suppresses hepatic molecular identity in damaged liver.
Article in Molecular systems biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
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- Mild oxidative stress and dietary epigenetic modulators direct DNA methylation remodeling toward stress-resilience pathways.BMC genomics · 2026Article
- ATF4 and CHOP coordinate endoplasmic reticulum stress-responsive gene programs through enhancer activation and chromatin looping.Nucleic acids research · 2026Article
- DNA damage/p53, innate immune, and unfolded protein responses are activated in primate liver after toxic, high-dose AAV-SMN1 delivery.Molecular therapy. Advances · 2026Article
- 125I inhibits the progression of cervical cancer by upregulating the HSF1/PU.1/SYK signaling pathway and consequently enhancing the apoptotic response mediated by ROS/USP7/P53.Scientific reports · 2025Article
- Influencing factors and mechanism of hepatocyte regeneration.Journal of translational medicine · 2025Review
- miRNA biomarkers to predict risk of primary non-function of fatty allografts and drug induced acute liver failures.Molecular and cellular biochemistry · 2025Article
- Targeting super-enhancers in liver cancer: from pathogenic mechanisms to clinical applications.Frontiers in pharmacology · 2025Review
- The role of SIRT1 in kidney diseases.International urology and nephrology · 2025Review
- Novel Optical Criteria and Mechanisms of Critical Decline in Liver Regenerative Potential.Cells · 2024Article
- Altered hepatic metabolic landscape and insulin sensitivity in response to pulmonary tuberculosis.PLoS pathogens · 2024Article
- Androgens Suppress Corticosteroid Binding Globulin in Male Mice, Affecting the Endocrine Stress Response.Endocrinology · 2024Article
- Adipose tissue macrophage infiltration and hepatocyte stress increase GDF-15 throughout development of obesity to MASH.Nature communications · 2024Article
- Ferroptosis and inflammation are modulated by the NFIL3-ACSL4 axis in sepsis associated-acute kidney injury.Cell death discovery · 2024Article
- O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts.Cell death & disease · 2024Article
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- Reduced Expression of Oligodendrocyte Linage-Enriched Transcripts During the Endoplasmic Reticulum Stress/Integrated Stress Response.ASN neuro · 2024Article
- Low-dose ethanol consumption inhibits neutrophil extracellular traps formation to alleviate rheumatoid arthritis.Communications biology · 2023Article
- An extended transcription factor regulatory network controls hepatocyte identity.EMBO reports · 2023Article
Corrections and comments
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Authors and funding
30 authors at 5 institutions in 4 countries.
Funding
Abstract
Liver injury triggers adaptive remodeling of the hepatic transcriptome for repair/regeneration. We demonstrate that this involves particularly profound transcriptomic alterations where acute induction of genes involved in handling of endoplasmic reticulum stress (ERS) is accompanied by partial hepatic dedifferentiation. Importantly, widespread hepatic gene downregulation could not simply be ascribed to cofactor squelching secondary to ERS gene induction, but rather involves a combination of active repressive mechanisms. ERS acts through inhibition of the liver-identity (LIVER-ID) transcription factor (TF) network, initiated by rapid LIVER-ID TF protein loss. In addition, induction of the transcriptional repressor NFIL3 further contributes to LIVER-ID gene repression. Alteration to the liver TF repertoire translates into compromised activity of regulatory regions characterized by the densest co-recruitment of LIVER-ID TFs and decommissioning of BRD4 super-enhancers driving hepatic identity. While transient repression of the hepatic molecular identity is an intrinsic part of liver repair, sustained disequilibrium between the ERS and LIVER-ID transcriptional programs is linked to liver dysfunction as shown using mouse models of acute liver injury and livers from deceased human septic patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.