Identification of candidate regulators of multipotency in human skeletal progenitor cells.

Stem cell differentiation is controlled intrinsically by dynamic networks of interacting lineage-specifying and multipotency genes. However, the relationship between internal genetic dynamics and extrinsic regulation of internal dynamics is complex and, in the case of skeletal progenitor cell differentiation, incompletely understood. In this study we elucidate a set of candidate markers of multipotency in human skeletal progenitor cells by systematic study of the relationships between gene expression and environmental stimulus. We used full genome cDNA microarrays to explore gene expression profiles in skeletal progenitor enriched populations derived from adult human bone marrow, minimally cultured in basal, osteogenic, chondrogenic, and adipogenic lineage-specifying culture conditions. We then used a variety of statistical clustering procedures to identify a small subset of genes which are related to these stromal lineages but are specific to none. For a selection of 11 key genes, conclusions of the microarray study were confirmed using quantitative real-time PCR.