title: ARID3A is required for mammalian placenta development.
abstract: Previous studies in the mouse indicated that ARID3A plays a critical role in the first cell fate decision required for generation of trophectoderm (TE). Here, we demonstrate that ARID3A is widely expressed during mouse and human placentation and essential for early embryonic viability. ARID3A localizes to trophoblast giant cells and other trophoblast-derived cell subtypes in the junctional and labyrinth zones of the placenta. Conventional Arid3a knockout embryos suffer restricted intrauterine growth with severe defects in placental structural organization. Arid3a null placentas show aberrant expression of subtype-specific markers as well as significant alteration in cytokines, chemokines and inflammatory response-related genes, including previously established markers of human placentation disorders. BMP4-mediated induction of trophoblast stem (TS)-like cells from human induced pluripotent stem cells results in ARID3A up-regulation and cytoplasmic to nuclear translocation. Overexpression of ARID3A in BMP4-mediated TS-like cells up-regulates TE markers, whereas pluripotency markers are down-regulated. Our results reveal an essential, conserved function for ARID3A in mammalian placental development through regulation of both intrinsic and extrinsic developmental programs.
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, United States; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rhee
authors.affiliation: Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States; Cell and Molecular Biology, Colorado State University, Fort Collins, CO 80523, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Dang
authors.affiliation: Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: June
authors.initials: J
authors.lastname: Harris
authors.affiliation: Cell and Molecular Biology, Colorado State University, Fort Collins, CO 80523, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Brown
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, United States; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Jonghwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, United States; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States. Electronic address: haleytucker@austin.utexas.edu.
authors.forename: Haley O
authors.initials: HO
authors.lastname: Tucker
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015726:Giant Cells / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology
chemical_list: C490798:ARID3A protein, human; C097532:Arid3a protein, mouse; C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D016207:Cytokines; D004268:DNA-Binding Proteins; D014157:Transcription Factors