Dynamic Organization of Cells in Colonic Epithelium is Encoded by Five Biological Rules

Abstract

Tissue organization is fundamental to the form and function of most, if not all, multicellular organisms. But what specifies the precise histologic organization of cells in tissues of plants and animals is unclear. We hypothesize that a tissue code exists that is the basis for dynamic maintenance of tissue organization. Any code for tissue organization must account for how the dynamics of tissue renewal maintain histologic structure. Accordingly, we modeled the dynamics of crypt renewal to determine how the organization of cells is maintained in colonic epithelium. Specifically, we modeled spatial and temporal asymmetries of cell division and established that five simple mathematical laws ([1] timing of cell division, [2] temporal order of cell division, [3] spatial direction of cell division, [4] number of cell divisions, and [5] cell lifespan) constitute a set of biological rules for colonic epithelia. Our results indicate that these rules form the basis of precise organization of cells in colonic epithelium during continuous crypt renewal. These five laws might even provide a means to understand the mechanisms that underlie organization of other tissue types, and how genetic alterations cause tissue disorganization that leads to birth defects and tissue pathology like cancer.