title: Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis.
abstract: Epithelial-mesenchymal interactions involve fundamental communication between tissues during organogenesis and are primarily regulated by growth factors and extracellular matrix. It is unclear whether RNA-containing exosomes are mobile genetic signals regulating epithelial-mesenchymal interactions. Here we identify that exosomes loaded with mesenchyme-specific mature microRNA contribute mobile genetic signals from mesenchyme to epithelium. The mature mesenchymal miR-133b-3p, loaded into exosomes, was transported from mesenchyme to the salivary epithelium, which did not express primary miR-133b-3p. Knockdown of miR-133b-3p in culture decreased endbud morphogenesis, reduced proliferation of epithelial KIT+progenitors, and increased expression of a target gene, Disco-interacting protein 2 homolog B (Dip2b). DIP2B, which is involved in DNA methylation, was localized with 5-methylcytosine in the prophase nucleus of a subset of KIT+progenitors during mitosis. In summary, exosomal transport of miR-133b-3p from mesenchyme to epithelium decreases DIP2B, which may function as an epigenetic regulator of genes responsible for KIT+progenitor expansion during organogenesis.
authors.affiliation: Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Toru
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Isabelle M A
authors.initials: IM
authors.lastname: Lombaert
authors.affiliation: Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Belinda R
authors.initials: BR
authors.lastname: Hauser
authors.affiliation: Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Vaishali N
authors.initials: VN
authors.lastname: Patel
authors.affiliation: Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: mhoffman@mail.nih.gov.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000166:cytology; D005456:Fluorescent Dyes / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis; D041681:NIH 3T3 Cells; D038081:Organogenesis; D034443:RNA Transport / Q000235:genetics*; D012469:Salivary Glands / Q000166:cytology / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D035683:MicroRNAs
keywords: 5-methylcytosine; DIP2B; KIT; epigenetic repression; epithelial-mesenchymal interaction; exosomes; miR-133b-3p; microRNA; progenitor cells; salivary gland