Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow.
Viable Lin(-) CD27(+) c-kit(Hi) Sca-1(Hi) GFP(+) cells recovered from heterozygous RAG1/GFP knockin mice progressed through previously defined stages of B, T, and NK cell lineage differentiation. In contrast to the GFP(-) cohort, there was minimal myeloid or erythroid potential in cells with an active RAG1 locus. Partial overlap with TdT(+) cells suggested that distinctive early lymphocyte characteristics are not synchronously acquired. Rearrangement of Ig genes initiates before typical lymphoid lineage patterns of gene expression are established, and activation of the RAG1 locus transiently occurs in a large fraction of cells destined to become NK cells. These early lymphocyte progenitors (ELP) are distinct from stem cells, previously described prolymphocytes, or progenitors corresponding to other blood cell lineages.
Igarashi
Hideya
H
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City 73104, USA.
Gregory
Sophia C
SC
Yokota
Takafumi
T
Sakaguchi
Nobuo
N
Kincade
Paul W
PW
D000483:Alleles; D000818:Animals; D000950:Antigens, Ly; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008164:Luminescent Proteins; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D014158:Transcription, Genetic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000950:Antigens, Ly; D015415:Biomarkers; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C064658:RAG-1 protein; D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit