State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Institute of Lifeomics, Beijing 102206, China.
Alkek Center for Molecular Discovery, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Genome Res. 2020 Feb;30(2):263-275. doi: 10.1101/gr.253328.119. Epub 2020 Feb 12.
Liver organogenesis and development are composed of a series of complex, well-orchestrated events. Identifying key factors and pathways governing liver development will help elucidate the physiological and pathological processes including those of cancer. We conducted multidimensional omics measurements including protein, mRNA, and transcription factor (TF) DNA-binding activity for mouse liver tissues collected from embryonic day 12.5 (E12.5) to postnatal week 8 (W8), encompassing major developmental stages. These data sets reveal dynamic changes of core liver functions and canonical signaling pathways governing development at both mRNA and protein levels. The TF DNA-binding activity data set highlights the importance of TF activity in early embryonic development. A comparison between mouse liver development and human hepatocellular carcinoma (HCC) proteomic profiles reveal 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 offers a panoramic view of mouse liver development and provides a rich resource to explore in-depth functional characterization.
肝脏发生和发育是一系列复杂的、协调良好的事件的组成。鉴定调控肝脏发育的关键因子和途径将有助于阐明生理和病理过程,包括癌症。我们对从小鼠胚胎 12.5 天(E12.5)到出生后第 8 周(W8)的肝组织进行了多维组学测量,包括蛋白质、mRNA 和转录因子(TF)DNA 结合活性,涵盖了主要的发育阶段。这些数据集揭示了核心肝脏功能和调控发育的经典信号通路在 mRNA 和蛋白质水平上的动态变化。TF DNA 结合活性数据集强调了 TF 活性在早期胚胎发育中的重要性。将小鼠肝脏发育与人类肝细胞癌(HCC)蛋白质组图谱进行比较,发现侵袭性更强的肿瘤的特征是早期胚胎发育途径的激活,而侵袭性较弱的肿瘤则维持成熟肝脏中升高的与肝脏功能相关的途径。这项工作提供了小鼠肝脏发育的全景图,并为深入探索功能特征提供了丰富的资源。