Zhejiang University School of Medicine, Hangzhou First People's Hospital, Hangzhou 310006, China.
Zhejiang University School of Medicine, Hangzhou 310058, China.
Int J Biol Sci. 2024 Jun 24;20(9):3544-3556. doi: 10.7150/ijbs.93739. eCollection 2024.
Hepatic progenitor cells (HPCs) have a bidirectional potential to differentiate into hepatocytes and bile duct epithelial cells and constitute a second barrier to liver regeneration in the adult liver. They are usually located in the Hering duct in the portal vein region where various cells, extracellular matrix, cytokines, and communication signals together constitute the niche of HPCs in homeostasis to maintain cellular plasticity. In various types of liver injury, different cellular signaling streams crosstalk with each other and point to the inducible transcription factor set, including FoxA1/2/3, YB-1, Foxl1, Sox9, HNF4α, HNF1α, and HNF1β. These transcription factors exert different functions by binding to specific target genes, and their products often interact with each other, with diverse cascades of regulation in different molecular events that are essential for homeostatic regulation, self-renewal, proliferation, and selective differentiation of HPCs. Furthermore, the tumor predisposition of adult HPCs is found to be significantly increased under transcriptional factor dysregulation in transcriptional analysis, and the altered initial commitment of the differentiation pathway of HPCs may be one of the sources of intrahepatic tumors. Related transcription factors such as HNF4α and HNF1 are expected to be future targets for tumor treatment.
肝祖细胞（HPCs）具有向肝细胞和胆管上皮细胞双向分化的潜能，构成成年肝脏再生的第二道屏障。它们通常位于门静脉区域的赫林管中，各种细胞、细胞外基质、细胞因子和通信信号共同构成 HPC 细胞的生态位，以维持细胞的可塑性。在各种类型的肝损伤中，不同的细胞信号流相互作用，并指向可诱导的转录因子集，包括 FoxA1/2/3、YB-1、Foxl1、Sox9、HNF4α、HNF1α 和 HNF1β。这些转录因子通过结合特定的靶基因发挥不同的功能，它们的产物经常相互作用，在不同的分子事件中存在着多样化的调控级联，这对于 HPCs 的稳态调节、自我更新、增殖和选择性分化是必不可少的。此外，在转录因子失调的转录分析中发现，成年 HPC 的肿瘤易感性显著增加，HPC 分化途径的初始承诺改变可能是肝内肿瘤的来源之一。相关的转录因子，如 HNF4α 和 HNF1，有望成为肿瘤治疗的未来靶点。
