A Time-resolved Multi-omic Atlas of the Developing Mouse Liver

Liver organogenesis and development is composed of a series of complex, well-orchestrated events. Identification of key factors and pathways governing liver development will help understand this process and may also provide insights for other physiological and pathological processes including cancer. For this purpose, we conducted multi-dimensional omics measurements including profiling of protein, mRNA, and transcription factor (TF) DNA binding activity from mouse liver tissues collected at embryonic day E12.5 to postnatal week W8, encompassing the major developmental stages to provide a molecular and integrative panoramic view of mouse liver development. These datasets revealed dynamic changes of core liver functions as well as canonical signaling pathways governing development at both mRNA and protein levels, and identified novel RNA splicing variants that are confirmed at the peptide level. The TF DNA binding activity dataset provided the first glimpse of liver development from four waves of TF activations and major TFs that may be responsible to drive the transcriptional program to govern liver development. A comparison between mouse liver development and human hepatocellular carcinoma (HCC) proteomic profiles revealed that more aggressive tumors are characterized with the activation of early embryonic development pathways, whereas less aggressive ones maintain liver-function related pathways that are elevated in the mature liver. This work provided a rich resource for liver development research community for future in-depth functional characterization.