title: Resolution of unique Sca-1highc-Kit- lymphoid-biased progenitors in adult bone marrow.
abstract: We have identified a distinctive lymphoid-restricted progenitor population in adult mouse bone marrow based on a unique c-Kit(-)Sca-1(high)Flt3(+) AA4(+) surface phenotype. These cells are highly lymphoid biased and rapidly generate B and T cells after adoptive transfer. However, whereas previously described lymphoid progenitors such as common lymphoid progenitors express TdT and relatively high levels of RAG2, and are enriched for cells with an active V(D)J recombinase, Flt3(+) AA4(+) cells within the c-Kit(-)Sca-1(high) bone marrow fraction are TdT(-), are RAG2(low), and do not display evidence for ongoing or past recombinase activity. Furthermore, unlike common lymphoid progenitors that readily generate B cells upon stimulation with IL-7, c-Kit(-)Sca-1(high)Flt3(+) precursors do not express abundant levels of the IL-7R, and require costimulation with Flt3 ligand and IL-7 to generate B cells in vitro. Moreover, these findings suggest that hematopoietic stem cells in adults generate an array of lymphoid-biased progenitor populations characterized by distinct gene expression and cytokine response profiles.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Harman
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Northrup
authors.forename: David
authors.initials: D
authors.lastname: Allman
mesh_terms: D000818:Animals; D000950:Antigens, Ly; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004253:DNA Nucleotidylexotransferase / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit; D011951:Receptors, Complement / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000276:immunology; D045567:VDJ Recombinases / Q000276:immunology; D051941:fms-Like Tyrosine Kinase 3 / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D004268:DNA-Binding Proteins; D015851:Interleukin-7; C074650:Ly6a protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C499308:Rag2 protein, mouse; D011951:Receptors, Complement; D020395:Receptors, Interleukin-7; C032402:complement 1q receptor; C084881:flt3 ligand protein; C497971:Flt3 protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3; D045567:VDJ Recombinases; D004253:DNA Nucleotidylexotransferase