Researchers pulled cell nuclei into microscopic glass tubes under controlled pressures and visualized the shear of the DNA and associated proteins by fluorescence microscopy. The study showed that nuclei in human embryonic stem cells were the most deformable, followed by hematopoietic stem cells, HSCs, that generate a wide range of blood and tissue cells. Both types of stem cells lack lamins A and C, two filamentous proteins that interact to stabilize the inner lining of the nucleus of most tissue cells. Lamins A and C stiffen cell nuclei and are expressed in cells only after gastrulation, when most stem cells generate the specific tissues of complex organisms.
The fluid-like character of the nucleus is shown to be set largely by the DNA and the DNA-attached proteins that form chromatin. The extent of deformation of the nucleus is further modulated by the lamina.
Understanding the sensitivity of stem cells and their nuclei to external stresses has very practical implications in handling these cells as well as in technologies such as cloning in which nuclei are manipulated, said Dennis Discher, a professor in Penns School of Engineering and Applied Science and the Penn School of Medicines Cell and Molecular Biology Graduate Group.
The study, published in the Oct. 2 issue of the Proceedings of the National Academy of Sciences, supports the theory that lamin proteins are responsible for much of the genomic lock-down within differentiated cells. Differentiated cells, typified by muscle cells, fat cells and bone cells, all arise from stem cells that have committed to these specialized cell types by l
|Contact: Jordan Reese|
University of Pennsylvania