Revealing the developmental origin and lineage predilection of neural progenitors within human bone marrow via single cell analysis: Implications for regenerative medicine

Human bone marrow stromal cells (BMSCs) are an easily accessible and expandable progenitor population with the capacity to generate neural cell types in addition to mesoderm. Lineage tracing studies in transgenic animals have indicated Nestin+ BMSCs to be descended from the truncal neural crest. Single cell analysis provides a means to identify the developmental origin and identity of human BMSC-derived neural progenitors when lineage tracing remains infeasible. This is a prerequisite towards translational application. This study suggested BMSCs originating from truncal neural crest to be the source of cells within long bone marrow possessing neural differentiation potential. Unraveling the transcriptomic dynamics of BMSC-derived neural progenitors promises to enhance differentiation efficiency and safety towards clinical application in cell therapy and disease modelling. Overall design: We attained transcriptomic profiles of embryonic long bone, adult human bone marrow, cultured BMSCs, and BMSC-derived neurospheres. Integrated scRNAseq analysis was supplemented by characterization of cells during culture expansion and following provision of growth factors and signaling agonists to bias lineage.