Abstract
Changes in the shape of the nuclear lamina are exhibited in senescent cells, as well as in cells expressing mutations in lamina genes. To identify cells with defects in the nuclear lamina we developed an imaging method that quantifies the intensity and curvature of the nuclear lamina. We show that this method accurately describes changes in the nuclear lamina. Spatial changes in nuclear lamina coincide with redistribution of lamin A proteins and local reduction in protein mobility in senescent cell. We suggest that local accumulation of lamin A in the nuclear envelope leads to bending of the structure. A quantitative distinction of the nuclear lamina shape in cell populations was found between fresh and senescent cells, and between primary myoblasts from young and old donors. Moreover, with this method mutations in lamina genes were significantly distinct from cells with wild-type genes. We suggest that this method can be applied to identify abnormal cells during aging, in in vitro propagation, and in lamina disorders.
Highlights
Cellular senescence refers to a decline in cell proliferation, initially described during in vitro propagation [1]
Cell senescence can be described by spatial changes in the nuclear lamina During in vitro propagation, the hMSCs undergo cellular senescence within a few passages and with an associated reduction in cell doubling [11,12,13]
Senescent hMSCs exhibit changes in the shape of the nuclear lamina [4] and the nuclear lamina is deformed in cells with high p16INK4a expression (Figure 1B)
Summary
Cellular senescence refers to a decline in cell proliferation, initially described during in vitro propagation [1]. In vivo senescent cells are suggested to promote biological processes that are associated with aging and cancer progression [2]. Cellular senescence is induced by numerous intra- and extra- cellular stimuli, which lead to changes in many cellular processes. A broad range of molecular markers is used to identify senescent cells [2]. Cellular senescence in marrow stroma cells (MSCs) is associated with spatial changes of the nuclear lamina [4]. Deformed nuclear structure is exhibited in aging and apoptosis [5,6], as well as in aging-associated cellular processes like apoptosis [7, 8]. Spatial changes of the nuclear lamina could be used to identify aging, apoptotic and senescent cells
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