Lin-Sca1+Kit- bone marrow cells contain early lymphoid-committed precursors that are distinct from common lymphoid progenitors

摘要

The significance of a population in mouse bone marrow of lineage negative, Sca1 positive, c-kit negative (LSK^-) cells, which is reported to be devoid of long-term repopulation capacity or myeloid potential, is unknown. Here, we show that the LSK^- population is composed of several subsets defined by the expression of flt3, CD25 and IL7Rα. The first subset was CD25^- and more than 90 % expressed either flt3, IL7Rα or both. The CD25^-LSK^- population had T, B and NK cell potential in vivo, and most of this activity was localized in the flt3⁺ subset, irrespective of the expression of IL7Rα. While lymphoid potential of flt3⁺LSK^- cells in vivo was threefold lower than that of lin^-Sca1^lokit^loIL7Rα⁺ common lymphoid progenitors (CLPs), their cloning efficiency in vitro was tenfold lower than that of CLPs. Furthermore, while the myeloid potential of flt3⁺LSK^- cells was tenfold lower than that of CLPs in the absence of M-CSF, the relative myeloid potential of both population was similar in its presence. These observations suggest differential growth factor requirements of both populations. The second subset of LSK^- cells was homogeneously CD25⁺⁺flt3^-IL7Rα⁺ and could be generated from both CD25^-LSK^- cells and from CLPs, but did not engraft in immunodeficient Rag1^-/- or Rag1^-/-γc^-/- hosts. This population, of which the significance is unclear, was increased in Rag1^-/- mice and in old mice. Thus, the LSK^- population is phenotypically and functionally heterogeneous and contains early lymphoid-committed precursors. Our findings imply that the early stages of lymphoid commitment are more complex than was thus far assumed.