Lin-Sca1+kit- bone marrow cells contain early lymphoid-committed precursors that are distinct from common lymphoid progenitors.
The significance of a population in mouse bone marrow of lineage-negative (Lin(-)), Sca1-positive, c-kit-negative (LSK(-)) cells, which is reported to be devoid of long-term repopulation capacity or myeloid potential, is unknown. In this study, we show that the LSK(-) population is composed of several subsets defined by the expression of flt3, CD25, and IL-7Ralpha. The first subset was CD25(-) and more than 90% expressed either flt3, IL-7Ralpha, or both. The CD25(-)LSK(-) population had T cell, B cell, and NK cell potential in vivo, and most of this activity was localized in the flt3(+) subset, irrespective of the expression of IL-7Ralpha. Although lymphoid potential of flt3(+)LSK(-) cells in vivo was 3-fold lower than that of lin(-)Sca1(low)kit(low)IL7Ralpha(+) common lymphoid progenitors (CLPs), their cloning efficiency in vitro was 10-fold lower than that of CLPs. Furthermore, although the myeloid potential of flt3(+)LSK(-) cells was 10-fold lower than that of CLPs in the absence of M-CSF, the relative myeloid potential of both populations 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(-)IL7Ralpha(+) and could be generated from both CD25(-)LSK(-) cells and from CLPs, but did not engraft in immunodeficient Rag1(-/-) or Rag1(-/-)gamma(c)(-/-) 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.
Kumar
Ritu
R
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Fossati
Valentina
V
Israel
Mason
M
Snoeck
Hans-Willem
HW
D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D002454:Cell Differentiation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019009:Proto-Oncogene Proteins c-kit; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000276:immunology
D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; C497971:Flt3 protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3