肝祖细胞（HPC）具有双向分化为肝细胞和胆管上皮细胞的潜力，并构成成人肝脏中肝再生的第二道屏障。它们通常位于门静脉区域的 Hering 管中，其中各种细胞、细胞外基质、细胞因子和通讯信号共同构成 HPC 的生态位，维持细胞的稳态，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串扰并指向诱导型转录因子集，包括 FoxA1/2/3、YB-1、Foxl1、Sox9、HNF4α、HNF1α 和 HNF1β。这些转录因子通过与特定靶基因结合来发挥不同的功能，并且它们的产物经常相互作用，在不同的分子事件中进行多种级联调节，这对于 HPC 的稳态调节、自我更新、增殖和选择性分化至关重要。此外，转录分析发现，在转录因子失调的情况下，成人HPCs的肿瘤易感性显着增加，HPCs分化途径的初始承诺改变可能是肝内肿瘤的来源之一。 HNF4α和HNF1等相关转录因子有望成为未来肿瘤治疗的靶标。©作者。

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.© The author(s).