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However, the molecular mechanisms underlying this maturation are not yet fully understood. In this study, YTHDC1 is identified as a key positive regulator of hepatocyte maturation and an essential factor in maintaining liver homeostasis. YTHDC1 expression increases in the liver after birth, and hepatocyte\u2010specific deletion of <jats:italic>Ythdc1<\/jats:italic> impairs hepatocyte maturation, leading to reduced liver weight, liver injury, inflammation, and fibrosis. These defects contribute to the development of nonalcoholic steatohepatitis and hepatocellular carcinoma in mice. YTHDC1 supports postnatal hepatocyte maturation and liver function by enhancing the expression of key transcription factors, FOXA1 and FOXA2, at the posttranscriptional level through m<jats:sup>6<\/jats:sup>A recognition. Restoring FOXA1 or FOXA2 expression mitigates the phenotypic defects observed in <jats:italic>Ythdc1<\/jats:italic>\u2010HKO mice. Mechanistically, YTHDC1 binds to the m<jats:sup>6<\/jats:sup>A regions of <jats:italic>Foxa1<\/jats:italic> and <jats:italic>Foxa2<\/jats:italic> mRNAs, promoting their expression. These findings reveal a mechanism by which YTHDC1 regulates hepatocyte maturation.<\/jats:p>","DOI":"10.1002\/advs.202505725","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T10:05:28Z","timestamp":1750327528000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["YTHDC1 Is Essential for Postnatal Liver Development and Homeostasis"],"prefix":"10.1002","volume":"12","author":[{"given":"Xinzhi","family":"Li","sequence":"first","affiliation":[{"name":"HIT Center for Life Sciences School of Life Science and Technology State Key Laboratory of Matter Behaviors in Space Environment Frontier Science Center for Interaction between Space Environment and Matter Zhengzhou Research Institute Harbin Institute of Technology  Harbin 150001 China"},{"name":"NHC Key Laboratory of Cell Transplantation The First Affiliated Hospital of Harbin Medical University  Harbin 150001 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