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Hypothesis: Caco-2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts.

ABSTRACT: Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco-2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco-2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single- to multi-cell ring/torus-shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well-described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders.

SUBMITTER: Zheng G

PROVIDER: S-EPMC6237597 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Hypothesis: Caco-2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts.

Zheng Gen G Kalinin Alexandr A AA Dinov Ivo D ID Meixner Walter W Zhu Shengtao S Wiley John W JW

Journal of cellular and molecular medicine 20180925 12

Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco-2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco-2 cells that appears to be driven by ac ...[more]

PMID: 30255651

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Project description:N-nitroso compounds (NOC) are genotoxic compounds and animal carcinogens, and may play a role in human cancer development. Since the gastro-intestinal tract is an important route of exposure, we hypothesize that NOC exposure targets genetic processes relevant in colon carcinogenesis. To investigate this, we analysed the transcriptomic effects of genotoxic concentrations of two nitrosamides, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 1ÂµM) and N-methyl-N-nitrosurea (MNU, 1mM), and four nitrosamines, N-nitrosodiethylamine (NDEA, 50mM), N-nitrosodimethylamine (NDMA, 100mM), N-nitrosopiperidine (NPIP, 40mM), and N-nitrosopyrrolidine (NPYR, 100mM), in the human colon carcinoma cell line Caco-2. Gene Ontology gene group, consensus motif gene group and biological pathway analysis revealed that nitrosamides had little effect on gene expression after 24 hours of exposure, whereas nitrosamines had a strong impact on the transcriptomic profile. Analyses showed modifications of cell cycle regulation and apoptosis pathways for nitrosamines which was supported by flow cytometric analysis. We found additional modifications in gene groups and pathways of oxidative stress and inflammation, which suggest an increase in oxidative stress and pro-inflammatory immune response upon nitrosamine exposure, although less distinct for NDMA. Furthermore, NDEA, NPIP and NPYR most strongly affected several developmental motif gene groups and pathways, which may influence developmental processes. Many of these pathways and gene groups are implicated in the carcinogenic process and their modulation by nitrosamine exposure may therefore influence the development of colon cancer. In summary, our study has identified pathway modifications in human colon cells which may be associated with cancer risk of nitrosamine exposure in the human colon. Keywords: Comparison of genome-wide gene expression between different conditions The study investigated differential gene expression in Caco-2 cell line mRNA following 24 hours of exposure to six different N-nitroso compounds. Four biological replicates per sample compound. One compound per array, hybridized against vehicle control. Dye-swap between biological replicates 1 and 2, and 3 and 4.

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Hypothesis: Caco-2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts.

Publications

Hypothesis: Caco-2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts.

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