Nuclei of human stem cells are soft and flexible, not hard

Washington, October 12 : Researchers at the University of Pennsylvania have found that the nuclei of human stem cells are soft and flexible, and not hard by nature.

This soft and flexible character of stem cell nuclei enables them to migrate through the body, and to adopt different shapes, say the researchers.

In a study, the researchers pulled cell nuclei into microscopic glass tubes under controlled pressures, and visualized the shear of the DNA and associated proteins by fluorescence microscopy.

They found 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.

The researchers have revealed that both types of stem cells lack lamins A and C, two filamentous proteins that 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 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.

Dennis Discher, a professor in Penn’s School of Engineering and Applied Science and the Penn School of Medicine, says that understanding the sensitivity of stem cells and their nuclei to external stresses has very practical implications in technologies such as cloning, wherein nuclei are manipulated

The study supports the theory that lamin proteins are responsible for much of the genomic lock-down within differentiated cells—muscle cells, fat cells and bone cells—which arise from stem cells that have committed to these specialized cell types by locking the DNA into a set pattern of gene expression.

With a view to verifying that lamin proteins were responsible for nuclear stiffness, the researchers created a line of epithelial cells in which lamin filaments had been almost eliminated.

Once as stiff as any other differentiated tissue cell derived from stem cells, the cell became as pliable as HSCs, say the researchers.

J. David Pajerowski, lead author and a graduate student in Penn’s School of Engineering and Applied Science, believes that controlling structural proteins within the nucleus might lead to new means for controlling genomic regulatory factors, and for generating stem cells from adult tissue cells.

The researchers have also found that over time, nuclear deformations in stem cells and hematopoietic cells become resistant to returning to their original shape, which provides evidence of plastic flow similar to that of wet clay in the hands of a sculptor.

They say that continued application of force eventually pulls nuclei into irreversible forms in which genes are re-arranged and massaged into new nuclear locations.

The findings have been reported in the Proceedings of the National Academy of Sciences. (ANI