DEVELOPMENTAL BIOLOGY: A Loss of Flexibility With Age

Beverly A. Purnell

As a cell transitions from an undifferentiated state to a differentiated cell type, its gene expression profile changes, which in part reflects physical changes in chromatin structure. In a complementary approach, Pajerowski et al. have examined the macroscopic properties of the nucleus during differentiation. Aspiration with a micropipette revealed that the nuclei of pluripotent human embryonic stem cells could be deformed relatively easily; however, as the cells differentiated, the nuclei became stiffer. Hematopoietic stem cells (from bone marrow) were able to differentiate into fewer cell types than embryonic stem cells and, similarly, showed an intermediate level of deformability. Progression toward the differentiated state was accompanied by an increase in the filamentous protein lamin A/C and greater condensation of chromatin. When lamin A/C was knocked down in epithelial cells, their flow behavior resembled that of hematopoietic stem cells. Further analysis showed that the fluid character of the nucleus is determined primarily by chromatin but that the degree of nuclear deformability is set by the lamina. Variations in the physical plasticity of the nucleus may be important for allowing less differentiated cells to move through tissues. — BAP

Proc. Natl. Acad. Sci. U.S.A. 104, 15619 (2007).

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