There is a wealth of data indicating human bone marrow derived stromal cells (HBMSCs) contain the skeletal stem cell (SSC) with the potential to differentiate along the osteogenic, adipogenic and chondrogenic lineages leading to significant interest as potential clinical therapies. However, despite these advances, current methods to isolate skeletal stem cells (SSCs) from human tissues are difficult as no single specific marker has been identified. Hence, limited understanding of SSC fate, immuno-phenotype and simple selection criteria proved to be limiting factors in the widespread clinical application of these cells. While a range of cell surface markers can enrich for SSCs, none of the proposed markers, alone, isolate single cells with the ability to form bone, cartilage, and adipose tissue in humans. In this work, we have developed a methodology to use oligonucleotide-coated gold nanoparticles to identify cells in human bone marrow displaying specific mRNA signatures to isolate and enrich for the SSCs.