脊椎动物肝脏是整合免疫和代谢互作的重要器官。文昌鱼肝盲囊被普遍认为是脊椎动物肝脏前体，且兼具类似肝脏的代谢和免疫功能，但是肝盲囊中是否具有脊椎动物肝脏样的免疫-代谢互相作用与调控尚不清楚。据此，我们提出“文昌鱼肝盲囊中存在类似脊椎动物肝脏的（固有）免疫-代谢互作和调控方式，即肝盲囊是整合免疫-代谢互作的先驱器官”这一假设。本申请就是要验证这一假设。拟开展的研究包括：1）利用转录组和代谢组分析，揭示免疫刺激和代谢刺激后肝盲囊中免疫和代谢相关基因的表达模式及代谢产物的变化；2）利用组学关联分析鉴定肝盲囊中参与免疫-代谢互作和调控的关键基因和信号通路；3）综合比较、分析上述结果，阐明肝盲囊中免疫-代谢互作和调控的机制及其与脊椎动物肝脏在免疫-代谢互作和调控方式上的异同。本研究将首次明确肝盲囊是否为整合免疫-代谢互作的先驱器官，极大丰富和提升对脊椎动物肝脏起源及其免疫-代谢互作和调控规律的认识。

Vertebrate liver is a representative organ that performs immune-metabolic interaction and regulation. Amphioxus is a basal chordate, whose hepatic caecum is generally considered as the precursor of vertebrate liver and possesses both liver-like metabolic and immunological functions. However，it is still unknown whether there are immune-metabolic interaction in hepatic caecum. Based on the similarity of hepatic caecum to liver, we thus hypothesized that “Amphioxus hepatic caecum may performs innate immune-metabolic interaction and regulation as the vertebrate liver does, namely the hepatic caecum is an evolutionary forerunner in the integration of innate immunity and metabolism.” To test this hypothesis, we plan to carry out the following researches: 1) Transcriptome and metabolome analysis to reveal how immune stimulus or metabolic perturbation modulates expression profiles of genes related to immunity and metabolism, as well as the change regularity of metabolite in hepatic caecum; 2) Transcriptome–metabolome association study to identify the key genes and signaling pathways involved in immune-metabolic interactions in the hepatic caecum; 3) The above results will be compared and analyzed comprehensively, to reveal the mechanism of immune-metabolic interactions and regulation in hepatic caecum, and clarify the similarities and differences of immune-metabolic interactions between hepatic caecum and liver. This work will certainly allow us to illuminate the origin and evolution of immune-metabolic interaction and regulation in vertebrate liver, and in addition, provide evidences to support or deny the notion that amphioxus hepatic caecum is the precursor of vertebrate liver, highly enriching and improving our understanding of the origin of vertebrate liver.