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    New quantitative approaches reveal the spatial preference of nuclear compartments in mammalian fibroblasts

    Weston, David J. and Russell, R.A. and Batty, E. and Jensen, K. and Stephens, D.A. and Adams, N.M. and Freemont, P.S. (2015) New quantitative approaches reveal the spatial preference of nuclear compartments in mammalian fibroblasts. Journal of The Royal Society Interface 12 (104), ISSN 1742-5689.

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    Abstract

    The nuclei of higher eukaryotic cells display compartmentalization and certain nuclear compartments have been shown to follow a degree of spatial organization. To date, the study of nuclear organization has often involved simple quantitative procedures that struggle with both the irregularity of the nuclear boundary and the problem of handling replicate images. Such studies typically focus on inter-object distance, rather than spatial location within the nucleus. The concern of this paper is the spatial preference of nuclear compartments, for which we have developed statistical tools to quantitatively study and explore nuclear organization. These tools combine replicate images to generate ‘aggregate maps' which represent the spatial preferences of nuclear compartments. We present two examples of different compartments in mammalian fibroblasts (WI-38 and MRC-5) that demonstrate new knowledge of spatial preference within the cell nucleus. Specifically, the spatial preference of RNA polymerase II is preserved across normal and immortalized cells, whereas PML nuclear bodies exhibit a change in spatial preference from avoiding the centre in normal cells to exhibiting a preference for the centre in immortalized cells. In addition, we show that SC35 splicing speckles are excluded from the nuclear boundary and localize throughout the nucleoplasm and in the interchromatin space in non-transformed WI-38 cells. This new methodology is thus able to reveal the effect of large-scale perturbation on spatial architecture and preferences that would not be obvious from single cell imaging.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): spatial point pattern analysis, nuclear compartments, spatial preference, thin-plate spline, intensity estimation, mammalian fibroblasts
    School: Birkbeck Schools and Departments > School of Business, Economics & Informatics > Computer Science and Information Systems
    Depositing User: David Weston
    Date Deposited: 09 Feb 2015 11:09
    Last Modified: 09 Feb 2015 11:10
    URI: http://eprints.bbk.ac.uk/id/eprint/11489

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