Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle

Three-dimensional suspension culture is a gravity-limited phenomenon. The b alancing forces necessary to keep the aggregates in suspension increase dir ectly with aggregate size. This leads to a self-propagating cycle of cell d amage by balancing forces. Cell culture in microgravity avoids this trade-o ff. We determined which genes mediate three-dimensional culture of cell and tissue aggregates in the low-shear stress, low-turbulent environment of ac tual microgravity. Primary cultures of human renal cortical cells were flow n on the space shuttle. Cells grown in microgravity and ground-based contro ls were grown for 6 days and fixed. RNA was extracted, and automated gene a rray analysis of the expression of 10,000 genes was performed. A select gro up of genes were regulated in microgravity. These 1,632 genes were independ ent of known shear stress response element-dependent genes and heat shock p roteins. Specific transcription factors underwent large changes in microgra vity including the Wilms' tumor zinc finger protein, and the vitamin D rece ptor. A specific group of genes, under the control of defined transcription factors, mediate three-dimensional suspension culture under microgravity c onditions.