PDF(Pubmed)
Abstract：
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.
摘要：
肝祖细胞（HPCs）具有向肝细胞和胆管上皮细胞分化的双向潜能，构成成年肝脏再生的第二屏障。它们通常位于门静脉区域的Hering导管中，在那里各种细胞，细胞外基质，细胞因子,和通信信号一起构成了稳态中HPCs的生态位，以维持细胞可塑性。在各种类型的肝损伤中，不同的细胞信号流相互串扰，并指向可诱导转录因子集，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，他们的产品经常相互作用，在不同的分子事件中具有不同的调节级联，这对于稳态调节是必不可少的，自我更新,扩散,和HPCs的选择性分化。此外，在转录分析中，发现成人HPCs的肿瘤易感性在转录因子失调下显著增加，HPCs分化途径的初始定型改变可能是肝内肿瘤的来源之一。HNF4α、HNF1等相关转录因子有望成为未来肿瘤治疗的靶点。
