title: The Transcription Factor ARID3a Is Important for In Vitro Differentiation of Human Hematopoietic Progenitors.
abstract: We recently reported that the transcription factor ARID3a is expressed in a subset of human hematopoietic progenitor stem cells in both healthy individuals and in patients with systemic lupus erythematosus. Numbers of ARID3a(+) lupus hematopoietic stem progenitor cells were associated with increased production of autoreactive Abs when those cells were introduced into humanized mouse models. Although ARID3a/Bright knockout mice died in utero, they exhibited decreased numbers of hematopoietic stem cells and erythrocytes, indicating that ARID3a is functionally important for hematopoiesis in mice. To explore the requirement for ARID3a for normal human hematopoiesis, hematopoietic stem cell progenitors from human cord blood were subjected to both inhibition and overexpression of ARID3a in vitro. Inhibition of ARID3a resulted in decreased B lineage cell production accompanied by increases in cells with myeloid lineage markers. Overexpression of ARID3a inhibited both myeloid and erythroid differentiation. Additionally, inhibition of ARID3a in hematopoietic stem cells resulted in altered expression of transcription factors associated with hematopoietic lineage decisions. These results suggest that appropriate regulation of ARID3a is critical for normal development of both myeloid and B lineage pathways.
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Ratliff
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD 20910;
authors.forename: Meenu
authors.initials: M
authors.lastname: Mishra
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;
authors.forename: Mark B
authors.initials: MB
authors.lastname: Frank
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;
authors.forename: Joel M
authors.initials: JM
authors.lastname: Guthridge
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; and Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 carol-webb@ouhsc.edu.
authors.forename: Carol F
authors.identifier: http://orcid.org/0000-0003-4164-9634
authors.initials: CF
authors.lastname: Webb
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005312:Fetal Blood; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: C490798:ARID3A protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors