Identification of Flt3+CD150− myeloid progenitors in adult mouse bone marrow that harbor T lymphoid developmental potential

Abstract

Common myeloid progenitors (CMPs) were first identified as progenitors that were restricted to myeloid and erythroid lineages. However, it was recently demonstrated that expression of both lymphoidand myeloid-related genes could be detected in myeloid progenitors. Furthermore, these progenitors were able to give rise to T and B lymphocytes, in addition to myeloid cells. Yet, it was not known whether these progenitors were multipotent at the clonogenic level or there existed heterogeneity within these progenitors with different lineage potential. Here we report that previously defined CMPs possess T-lineage potential, and that this is exclusively found in the Flt3 ؉ CD150 -subset of CMPs at the clonal level. In contrast, we did not detect B-lineage potential in CMP subsets. Therefore, these IntroductionAll blood lineages ultimately arise from hematopoietic stem cells (HSCs). HSCs, along with downstream multipotent progenitors (MPPs) and lymphoid-primed MPPs (LMPPs), are present within a small pool of bone marrow (BM) cells with the surface phenotype of LSK (Lineage-marker Ϫ Sca1 ϩ Kit ϩ ). 1,2 Outside of LSK progenitors, a population of BM progenitors characterized as Lin -Sca1 -Kit ϩ CD34 ϩ Fc␥R low was found to be able to give rise to myeloid or erythroid cells, but appeared to lack the ability to generate lymphoid cells in in vivo and in vitro assays. 3 Thus it appeared these cells were restricted to myeloid/erythroid lineages. Because myeloid and erythroid potential was present at the clonogenic level within this population, these progenitors were termed common myeloid progenitors, or CMPs. 3 Granulocyte/monocyte progenitors (GMPs) and megakaryocyte/erythrocyte progenitors (MEPs) were also identified. As GMPs and MEPs possessed a more restricted developmental potential than CMPs, it was postulated that GMPs and MEPs were downstream of CMPs and that CMPs gave rise to myeloid cells or erythroid cells via GMPs or MEPs, respectively. 3 More recent work has suggested that a degree of lymphoid potential persists in myeloid progenitors. First, myeloid progenitors transduced with stabilized ␤-catenin were able to give rise to T and B lymphocytes. 4 Using Ikaros-reporter mice, 5 expression of both lymphoid-and myeloid-related genes was detected in Lin -Sca1 -Kit ϩ GFP Ikarosϩ BM cells, suggesting the existence of lymphoidmyeloid progenitors within the previously thought myeloid/ erythroid-restricted progenitor compartment. 6 It was further shown that some of these progenitors were able to give rise to T and B lymphocytes, in addition to myeloid cells, at the population level. 6 However, it was not known whether individual cells within this population were multipotent at the clonal level. Alternatively, there might be heterogeneity within this population where subsets of progenitors possess different lineage potentials. Indeed, recent work has clearly established heterogeneity for myeloid and erythroid lineage potentials among CMPs. CMPs can be subdivided into CD150 -(preGM) and CD150 ϩ (preMegE) populations, with ...

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