Viviane Galvão a,b, José G. V. Miranda b, Roberto F. S. Andrade b, José S. Andrade Jr.c,d, Lazaros K. Gallos e, and Hernán A. Makse e,1
-Author Affiliations
aDepartamento de Ciências Biológicas, Universidade Estadual de Feira de Santana, 44036-900, Feira de Santana, Bahia, Brazil;
bInstituto de Física, Universidade Federal da Bahia, 40210-210, Salvador, Bahia, Brazil;
cDepartamento de Física, Universidade Federal do Ceará, Campus do Pici, 60451–970, Fortaleza, Ceara, Brazil;
dIfB, HIF E12, ETH Honggerberg, 8093 Zurich, Switzerland; and
eLevich Institute and Physics Department, City College of New York, New York, NY 10031
Edited by H. Eugene Stanley, Boston University, Boston, MA, and approved February 4, 2010 (received for review December 22, 2009)
Abstract
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.
complex network modular organization self-similarity stem cells
Footnotes
1To whom correspondence should be addressed. E-mail:hmakse@lev.ccny.cuny.edu.
Author contributions: V.G., J.M., R.F.S.A., J.S.A.J., L.K.G., and H.A.M. designed research, performed research, analyzed data, and wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0914748107/DCSupplemental.
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