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Quantification of the Spatial Organization of the Nuclear Lamina as a Tool for Cell Classification

  • Righolt C
  • Zatreanu D
  • Raz V
ISRN Molecular Biology (2013) 2013 1-6
DOI: 10.1155/2013/374385
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Abstract

The nuclear lamina is the structural scaffold of the nuclear envelope that plays multiple regulatory roles in chromatin organization and gene expression as well as a structural role in nuclear stability. The lamina proteins, also referred to as lamins, determine nuclear lamina organization and define the nuclear shape and the structural integrity of the cell nucleus. In addition, lamins are connected with both nuclear and cytoplasmic structures forming a dynamic cellular structure whose shape changes upon external and internal signals. When bound to the nuclear lamina, the lamins are mobile, have an impact on the nuclear envelop structure, and may induce changes in their regulatory functions. Changes in the nuclear lamina shape cause changes in cellular functions. A quantitative description of these structural changes could provide an unbiased description of changes in cellular function. In this review, we describe how changes in the nuclear lamina can be measured from three-dimensional images of lamins at the nuclear envelope, and we discuss how structural changes of the nuclear lamina can be used for cell classification.

Figures

  • Figure 1: (a) Confocal microscopy images of living cells expressing LMNA fused to GFP in human mesenchymal stem cells (cross-sections are shown). LMNA-GFP transgene was expressed in cells by a lentivirus expression system. Spatial changes in the structure of the nuclear lamina are shown in a lateral (x,y)-plane and in a (x,z)-plane. The top shows a typical nucleus of an early passage from a 35-year-old donor. Bottom left shows a nucleus from the same donor but at a late passage number. This exemplifies how the nuclear lamina structure changes in senescent cells. Bottom right panel depicts a typical nucleus of an early passage cell from an 81-year-old donor. (b) LMNA is redistributed at the nuclear lamina concurrent with the change in the shape. The “even distribution” at the “short edges” of the structure in young cells (upper left) becomes more heterogeneous along the nuclear lamina for the older cell (bottom left). Protein accumulation is illustrated with red for high values and blue for low values; the color scale is linear. The curvature of the lamina locally increases along the structure (lower right) compared to the young cell (upper right). Red indicates high curvature values and blue low values; the scale is logarithmic.The sections shown match the cross-sections in (a).
  • Figure 2: LMNA accumulation on the nuclear envelop is enriched in senescent cells. (a) Images of representative nuclei show LMNA staining in WI38 fibroblasts at early and late passage number (passage 13 and 27, resp.). Cells were mock treated or treated with 1% triton prior to fixation. LMNA is visualized with mouse-antibodies in red, and the DNA is counterstained with DAPI. After triton treatment, heterochromatic foci are disrupted. LMNA fluorescent intensities over the lines through the nuclei are shown in the lower figures. (b) LMNA enrichment at the nuclear envelope. LMNA enrichment at the nuclear envelop is normalized to the LMNA signal across the nucleus. Means and standard deviations are shown for 100 nuclei.
  • Figure 3: Cell classification of human mesenchymal stem cells at passage 4 (PS 4; blue circles) and passage 9 (PS 9; red squares) based on the normalized curvature and intensity. A linear classifier—the black line in the scatter plot—separates the two cell types with an error rate of 13% (see [18] for technical details). These features can be used to discriminate between the younger and older cells.
  • Figure 4: Normalized curvature and intensity measurements for a variety of cell populations are summarized. LMNA redistributes for aging and senescence, this is associated with a decrease in normalized intensity. Apoptotic cells undergo a severe morphological change, which is reflected in the increased curvature values. Apoptosis can be achieved either directly from healthy states or indirectly from old or senescent cells, adapted from [15].

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CITATION STYLE

APA

Righolt, C. H., Zatreanu, D. A., & Raz, V. (2013). Quantification of the Spatial Organization of the Nuclear Lamina as a Tool for Cell Classification. ISRN Molecular Biology, 2013, 1–6. https://doi.org/10.1155/2013/374385

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