Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC) and hydroxymethylation (5hmC) are highly dynamic during early embryonic development, less is known about their roles at later stages of differentiation. Using an in vitro model of hepatocyte differentiation, we show here that 5hmC precedes the expression of promoter 1 (P1)-dependent isoforms of HNF4A, a master transcription factor of hepatocyte identity. 5hmC and HNF4A expression from P1 are dependent on ten-eleven translocation (TET) dioxygenases. In turn, the liver pioneer factor FOXA2 is necessary for TET1 binding to the P1 locus. Both FOXA2 and TETs are required for the 5hmC-related switch in HNF4A expression. The epigenetic event identified here may be a key step for the establishment of the hepatocyte program by HNF4A.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511103 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2017.05.023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Human liver organoids are susceptible to Plasmodium vivax infection.
Malar J
December 2024
Siriraj Integrative Center for Neglected Parasitic Diseases, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Background: The eradication of Plasmodium vivax malaria is complicated due to the presence of hypnozoites, the hidden dormant form of the parasite that is present in the liver. Currently available drug regimens are effective at killing hypnozoites but cause side effects and are difficult to administer. Studies testing drugs for liver-stage malaria remain rare and mainly rely on the use of cancerous or immortalized hepatic cells and primary hepatocytes.
View Article and Find Full Text PDFDecreased lncRNA HNF4A-AS1 facilitates resistance to sorafenib-induced ferroptosis of hepatocellular carcinoma by reprogramming lipid metabolism.
Theranostics
December 2024
Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Resistance to sorafenib remains a major challenge in the systemic therapy of liver cancer. However, the involvement of lipid metabolism-related lncRNAs in this process remains unclear. Different expression levels of lipid metabolism-related lncRNAs in HCC were compared by analysis of Gene Expression Omnibus and The Cancer Genome Atlas databases.
View Article and Find Full Text PDFInvestigating gene expression datasets of hippocampus tissue to discover Alzheimer's disease-associated molecular markers.
J Alzheimers Dis
December 2024
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
Background: Alzheimer's disease (AD) is an advancing neurodegenerative disorder distinguished by the formation of amyloid plaques and neurofibrillary tangles in the human brain. Nevertheless, the lack of peripheral biomarkers that can detect the development of AD remains a significant limitation.
Objective: The main aim of this work was to discover the molecular markers associated with AD.
Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids.
Nat Commun
November 2024
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, Utrecht, the Netherlands.
Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic 'fetal' and WNT-high 'embryonal', displaying divergent WNT signaling patterns.
View Article and Find Full Text PDFMetastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.
Elife
November 2024
Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, United States.
Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here, we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!