There is a wealth of data indicating human bone marrow contains skeletal stem
cells (SSC) with the capacity for osteogenic, chondrogenic and adipogenic
differentiation. However, current methods to isolate SSCs are restricted by the
lack of a defined marker, limiting understanding of SSC fate, immunophenotype,
function and clinical application. The current study applied single-cell
RNA-sequencing to profile human adult bone marrow populations from 11 donors and
identified novel targets for SSC enrichment. Spherical nucleic acids were used
to detect these mRNA targets in SSCs. This methodology was able to rapidly
isolate potential SSCs found at a frequency of <1 in 1,000,000 in human bone
marrow, with the capacity for tri-lineage differentiation in vitro and ectopic
bone formation in vivo. The current studies detail the development of a platform
to advance SSC enrichment from human bone marrow, offering an invaluable
resource for further SSC characterisation, with significant therapeutic impact
therein.