Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression.
The Runx1/core binding factor-beta (CBFbeta) transcriptional complex is required for the establishment of hematopoiesis during development. Despite its critical role during development, a detailed analysis of Runx1 expression within specific lineages and developmental stages of the adult hematopoietic system is lacking. To address this, we have developed a Runx1-green fluorescent protein (GFP) knock-in mouse. We show that Runx1 is expressed in several hematopoietic lineages, including myeloid, B-lymphoid, and T-lymphoid cells. By contrast, Runx1 is weakly expressed in early erythroid cells, and its expression is rapidly extinguished during later stages of erythropoiesis. Runx1 expression is induced during early B-cell development and is expressed at a uniform level during all subsequent stages of B-cell development. Within the thymus, Runx1 is expressed at the highest level in CD4-CD8- double-negative thymocytes. In peripheral T cells, Runx1 is differentially expressed, with CD4+ T cells expressing 2- to 3-fold higher levels of Runx1 than CD8+ cells. Taken together, these findings indicate that although widely expressed in the hematopoietic system, the expression of Runx1 is regulated in a cell type- and maturation stage-specific manner. In addition, the Runx1-IRES-GFP knock-in mouse strain should prove valuable for investigation of Runx1 function in adult hematopoiesis.
Lorsbach
Robert B
RB
Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. robert.lorsbach@stjude.org
Moore
Jennifer
J
Ang
Sonny O
SO
Sun
Weili
W
Lenny
Noel
N
Downing
James R
JR
D000328:Adult; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D005838:Genotype; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008198:Lymph Nodes / Q000502:physiology; D016131:Lymphocyte Subsets / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; D014157:Transcription Factors; D049452:Green Fluorescent Proteins