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A time-resolved multi-omic atlas of the developing mouse liver.
Tongqing Gong1, Chunchao Zhang2, Xiaotian Ni1,3
1State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Institute of Lifeomics, Beijing 102206, China.
Genome Research
|February 14, 2020
Summary
This study maps mouse liver development using multi-omics data, revealing early embryonic pathways linked to aggressive liver cancer (hepatocellular carcinoma). It provides a resource for understanding liver development and disease.
Area of Science:
- Developmental Biology
- Molecular Biology
- Oncology
Background:
- Liver organogenesis involves complex, orchestrated events crucial for physiological functions.
- Understanding liver development aids in elucidating pathological processes, including cancer.
- Key factors and pathways governing liver development require comprehensive identification.
Purpose of the Study:
- To comprehensively map mouse liver development across major life stages using multidimensional omics.
- To identify dynamic changes in core liver functions and signaling pathways during development.
- To compare developmental profiles with human hepatocellular carcinoma (HCC) to understand cancer progression.
Main Methods:
- Multidimensional omics measurements (protein, mRNA, transcription factor DNA-binding activity) were performed on mouse liver tissues.
- Samples were collected from embryonic day 12.5 to postnatal week 8, covering key developmental stages.
- Proteomic profiles of mouse liver development were compared with human HCC patient data.
Main Results:
- Dynamic changes in mRNA, protein levels, and transcription factor activity were observed throughout liver development.
- Canonical signaling pathways governing liver development showed dynamic regulation at both mRNA and protein levels.
- Aggressive HCC tumors showed activation of early embryonic development pathways, unlike less aggressive tumors that maintained mature liver pathways.
Conclusions:
- Multidimensional omics data provide a panoramic view of mouse liver development.
- Transcription factor activity is critical during early embryonic liver development.
- Aberrant activation of developmental pathways correlates with aggressive hepatocellular carcinoma, offering insights into disease mechanisms.
