title: Identification of the proliferation/differentiation switch in the cellular network of multicellular organisms.
abstract: The protein-protein interaction networks, or interactome networks, have been shown to have dynamic modular structures, yet the functional connections between and among the modules are less well understood. Here, using a new pipeline to integrate the interactome and the transcriptome, we identified a pair of transcriptionally anticorrelated modules, each consisting of hundreds of genes in multicellular interactome networks across different individuals and populations. The two modules are associated with cellular proliferation and differentiation, respectively. The proliferation module is conserved among eukaryotic organisms, whereas the differentiation module is specific to multicellular organisms. Upon differentiation of various tissues and cell lines from different organisms, the expression of the proliferation module is more uniformly suppressed, while the differentiation module is upregulated in a tissue- and species-specific manner. Our results indicate that even at the tissue and organism levels, proliferation and differentiation modules may correspond to two alternative states of the molecular network and may reflect a universal symbiotic relationship in a multicellular organism. Our analyses further predict that the proteins mediating the interactions between these modules may serve as modulators at the proliferation/differentiation switch.
authors.affiliation: The Chinese Academy of Sciences Key Laboratory of Developmental Biology, Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xia
authors.forename: Huiling
authors.initials: H
authors.lastname: Xue
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.forename: Jiamu
authors.initials: J
authors.lastname: Wang
authors.forename: Qingpeng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
authors.forename: Jing-Dong J
authors.initials: JD
authors.lastname: Han
mesh_terms: D000818:Animals; D001695:Biology; D002454:Cell Differentiation; D049109:Cell Proliferation; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D030562:Databases, Protein; D004331:Drosophila melanogaster; D006801:Humans; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry*; D040901:Proteomics / Q000379:methods; D049490:Systems Biology / Q000379:methods*; D014158:Transcription, Genetic
chemical_list: D011506:Proteins