Stem cells respond to environmental signals that induce their differentiation to cells that make up specialized tissues and organs. Our laboratory has focused on bone marrow mesenchymal stem cells (MSCs) that supply bone osteoblasts and marrow adipocytes, an output that appears to be reciprocal. Case in point: exercise promotes osteogenesis and bone formation, and inhibits marrow adipose accrual. A mechanically induced signal pathway concentrating on preserving β-catenin also causes increased structure of the actin cytoskeleton, both of which inhibit adipogenesis. Recently we showed that intranuclear actin is as important to MSC lineage decisions as cytoplasmic actin. This opens up new areas for understanding gene expression in stem cells.