Departamento de Ciências Biológicas, Universidade Estadual de Feira de Santana, 44036-900, Feira de Santana, Bahia, Brazil.
Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5750-5. doi: 10.1073/pnas.0914748107. Epub 2010 Mar 10.
Cell differentiation in multicellular organisms is a complex process whose mechanism can be understood by a reductionist approach, in which the individual processes that control the generation of different cell types are identified. Alternatively, a large-scale approach in search of different organizational features of the growth stages promises to reveal its modular global structure with the goal of discovering previously unknown relations between cell types. Here, we sort and analyze a large set of scattered data to construct the network of human cell differentiation (NHCD) based on cell types (nodes) and differentiation steps (links) from the fertilized egg to a developed human. We discover a dynamical law of critical branching that reveals a self-similar regularity in the modular organization of the network, and allows us to observe the network at different scales. The emerging picture clearly identifies clusters of cell types following a hierarchical organization, ranging from sub-modules to super-modules of specialized tissues and organs on varying scales. This discovery will allow one to treat the development of a particular cell function in the context of the complex network of human development as a whole. Our results point to an integrated large-scale view of the network of cell types systematically revealing ties between previously unrelated domains in organ functions.
多细胞生物中的细胞分化是一个复杂的过程,可以通过还原论的方法来理解,即识别控制不同细胞类型生成的各个过程。或者,可以采用大规模的方法寻找生长阶段的不同组织特征,有望揭示其模块化的全局结构,目标是发现细胞类型之间以前未知的关系。在这里,我们对大量分散的数据进行分类和分析,基于从受精卵到发育成熟的人类的细胞类型(节点)和分化步骤(链接),构建人类细胞分化网络(NHCD)。我们发现了一个临界分支的动力学规律,揭示了网络模块化组织中的自相似规律,使我们能够在不同的尺度上观察网络。出现的画面清楚地识别出按照层次组织排列的细胞类型簇,范围从亚模块到专门组织和器官的超模块,规模各不相同。这一发现将使人们能够将特定细胞功能的发展置于人类发育这一复杂网络的背景下进行整体处理。我们的结果指向一个整体的、大规模的细胞类型网络视图,系统地揭示了器官功能中以前不相关领域之间的联系。