title: Differential expression of the transcription factor ARID3a in lupus patient hematopoietic progenitor cells.
abstract: Although hematopoietic stem/progenitor cells (HSPCs) are used for transplantation, characterization of the multiple subsets within this population in humans has lagged behind similar studies in mice. We found that expression of the DNA-binding protein, ARID3a, in mouse stem cells was important for normal development of hematopoietic lineages; however, progenitors expressing ARID3a in humans have not been defined. We previously showed increased numbers of ARID3a(+) B cells in nearly half of systemic lupus erythematosus (SLE) patients, and total numbers of ARID3a(+) B cells were associated with increased disease severity. Because expression of ARID3a in those SLE patients occurred throughout all B cell subsets, we hypothesized that ARID3a expression in patient HSPCs might also be increased relative to expression in healthy controls. Our data now show that ARID3a expression is not limited to any defined subset of HSPCs in either healthy controls or SLE patients. Numbers of ARID3a(+) HSPCs in SLE patients were increased over numbers of ARID3a(+) cells in healthy controls. Although all SLE-derived HSPCs exhibited poor colony formation in vitro compared with controls, SLE HSPCs with high numbers of ARID3a(+) cells yielded increased numbers of cells expressing the early progenitor marker, CD34. SLE HSPCs with high numbers of ARID3a(+) cells also more readily generated autoantibody-producing cells than HSPCs with lower levels of ARID3a in a humanized mouse model. These data reveal new functions for ARID3a in early hematopoiesis and suggest that knowledge regarding ARID3a levels in HSPCs could be informative for applications requiring transplantation of those cells.
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Ratliff
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; Microbiology and Immunology Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104;
authors.forename: Julie M
authors.initials: JM
authors.lastname: Ward
authors.affiliation: Clinical Pharmacology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.affiliation: Microbiology and Immunology Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; and.
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; Microbiology and Immunology Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 carol-webb@omrf.org.
authors.forename: Carol F
authors.initials: CF
authors.lastname: Webb
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008875:Middle Aged; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C490798:ARID3A protein, human; D000974:Antibodies, Antinuclear; D000954:Antigens, Surface; D004268:DNA-Binding Proteins; D014157:Transcription Factors