Boman Bruce M, Dinh Thien-Nam, Decker Keith, Emerick Brooks, Modarai Shirin R, Opdenaker Lynn M, Fields Jeremy Z, Raymond Christopher, Schleiniger Gilberto
Department of Mathematical Sciences, Center for Applications of Mathematics in Medicine, Newark, Delaware, USA.
Department of Computer & Information Sciences, University of Delaware, Newark, Delaware, USA.
Biol Cell. 2025 Jul;117(7):e70017. doi: 10.1111/boc.70017.
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.
组织构成对于大多数（即便不是全部）多细胞生物的形态和功能而言至关重要。但究竟是什么决定了动植物组织中细胞精确的组织学构成尚不清楚。我们推测存在一种组织编码，它是组织构成动态维持的基础。任何组织构成编码都必须解释组织更新的动态过程是如何维持组织结构的。因此，我们对隐窝更新的动态过程进行建模，以确定结肠上皮中细胞的构成是如何得以维持的。具体而言，我们对细胞分裂的空间和时间不对称性进行建模，并确定了五条简单的数学法则（[1]细胞分裂时间，[2]细胞分裂的时间顺序，[3]细胞分裂的空间方向，[4]细胞分裂次数，以及[5]细胞寿命）构成了一套结肠上皮的生物学规则。我们的结果表明，这些规则构成了结肠上皮在隐窝持续更新过程中细胞精确构成的基础。这五条法则甚至可能为理解其他组织类型构成的潜在机制，以及基因改变如何导致组织紊乱进而引发出生缺陷和诸如癌症等组织病变提供一种途径。
