Clonal barcoding of endogenous adult hematopoietic stem cells reveals a spectrum of lineage contributions
The hierarchical model of hematopoiesis posits that self-renewing, multipotent hematopoietic stem cells (HSCs) give rise to all blood cell lineages. While this model accounts for hematopoiesis in transplant settings, its applicability to steady-state hematopoiesis remains to be clarified. Here we used inducible clonal DNA barcoding of endogenous adult HSCs to trace their contribution to major hematopoietic cell lineages in unmanipulated animals. Whereas the majority of barcodes were unique to a single lineage, we also observed frequent barcode sharing between multiple lineages, specifically between lymphocytes and myeloid cells. These results suggest a spectrum of multipotent and unipotent HSCs that collectively drive continuous hematopoiesis in the adult, and highlight a close relationship of myeloid and lymphoid development. Overall design: For transposon integration site cloning, bone marrow cells and thymocytes were isolated from the Pdzk1ip1CreERR26FlipJump mice at months 6 and 10 post tamoxifen induction. Granulocytes, monocytes, MPP, MkP, EryP, ImmB, DN and DP were sorted from isolated bone marrow cells and thymocytes.