single cell RNA seq of mouse bone marow-derived hematopoietic stem progenitor cells

Hematopoietic stem cells (HSCs) have been considered to progressively lose the self-renewal and differentiation potentials towards the commitment to each blood lineage. However, recent studies have suggested megakaryocyte progenitors are generated in a close relation with HSCs. In this study, we identified CD201-CD48- or CD48+ CD150+CD34-Kit+Sca-1+Lin- cells as new early megakaryocyte progenitors (MegP) in adult mouse bone marrow by single-cell (sc) transplantation, sc colony assay, sc RT-PCR, and sc RNA-sequencing. These MegP had little repopulating potential in vivo but formed megakaryocyte colonies in vitro. Transcriptome analysis suggested that these MegP lie downstream of HSCs and upstream of multipotent progenitors in a megakaryocyte differentiation pathway. The polyinosinic-polycytidylic acid (polyIC) injection and long-term reconstitution data suggested that a proportion of MegP expand after inflammation and transplantation. Here we propose a new model of HSC differentiation where HSCs give rise to common myeloid progenitors and MegP with little repopulating activity. Overall design: scRNA-Seq were successfully performed on 48 HSC1-P1 cells, 48 HSC1-P2cells, 44 HSC1-P3 cells, 44 HPC1-P1 cells, 48 HPC1-P2 cells, 44 HPC1-P3 cells, and 48 MPP2 cells.