Modularity map of the network of human cell differentiation

TL;DR

This paper constructs and analyzes a large-scale network of human cell differentiation, revealing a fractal, hierarchical modular structure that offers new insights into the organization of cell types and developmental processes.

Contribution

It introduces a network-based large-scale approach to understanding human cell differentiation, uncovering a fractal modular organization and hierarchical clustering of cell types.

Findings

Discovery of a dynamical law of critical branching in the network.

Identification of hierarchical clusters of cell types from sub-modules to super-modules.

Revealing a fractal regularity in the modular organization of cell differentiation.

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 crying baby. We discover a dynamical law of critical branching, which reveals a fractal 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.