Single-cell transcriptomics of cultured skeletal stem cells with a PDGFRbeta D849V mutation. Single-cell transcriptomics of cultured skeletal stem cells with a PDGFRbeta D849V mutation

We demonstrate that skeletal stem cells (SSCs) isolated from mice with a gain-of-function D849V point mutation in PDGFRbeta exhibit colony formation defects that parallel the wasting or overgrowth phenotypes of the mice. Single-cell RNA transcriptomics with SSC-derived polyclonal colonies was performed to characterize single-cell differentiation potential and molecular signatures. This study indicates multi-lineage potential of cultured SSCs and identifies molecular alterations in osteogenic and chondrogenic precursors. Overall design: Single-cell RNA sequencing of sorted and cultured PDGFRalpha+/Sca-1+ skeletal stem cells of 3-weeks-old limb of four genotypes (STAT1+/-, STAT1-/-, PDGFRbD849V+/-STAT1+/-,PDGFRbD849V+/-STAT1-/-) of mice