title: Lgr5 Marks Neural Crest Derived Multipotent Oral Stromal Stem Cells.
abstract: It has been suggested that multipotent stem cells with neural crest (NC) origin persist into adulthood in oral mucosa. However their exact localization and role in normal homeostasis is unknown. In this study, we discovered that Lgr5 is expressed in NC cells during embryonic development, which give rise to the dormant stem cells in the adult tongue and oral mucosa. Those Lgr5 positive oral stromal stem cells display properties of NC stem cells including clonal growth and multipotent differentiation. RNA sequencing revealed that adult Lgr5+ oral stromal stem cells express high number of neural crest related markers like Sox9, Twist1, Snai1, Myc, Ets1, Crabp1, Epha2, and Itgb1. Using lineage-tracing experiments, we show that these cells persist more than a year in the ventral tongue and some areas of the oral mucosa and give rise to stromal progeny. In vivo transplantation demonstrated that these cells reconstitute the stroma. Our studies show for the first time that Lgr5 is expressed in the NC cells at embryonic day 9.5 (E9.5) and is maintained during embryonic development and postnataly in the stroma of the ventral tongue, and some areas of the oral mucosa and that Lgr5+ cells participate in the maintenance of the stroma.
authors: Department of Otolaryngology, Head & Neck Surgery, University of Southern California, Los Angeles, California, USA.|Department of Biochemistry and Molecular Biology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors: Keerthi
authors: K
authors: Boddupally
authors: Department of Otolaryngology, Head & Neck Surgery, University of Southern California, Los Angeles, California, USA.|Department of Biochemistry and Molecular Biology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors: Guangfang
authors: G
authors: Wang
authors: Norris Medical Library, University of Southern California, Los Angeles, California, USA.
authors: Yibu
authors: Y
authors: Chen
authors: Department of Otolaryngology, Head & Neck Surgery, University of Southern California, Los Angeles, California, USA.|Department of Biochemistry and Molecular Biology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.|Centre of New Technologies, University of Warsaw, Warsaw, Poland.
authors: Agnieszka
authors: A
authors: Kobielak
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D009055:Mouth / Q000166:cytology / Q000254:growth & development; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000254:growth & development; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled
keywords: Mesenchymal stem cells; Somatic stem cells; Stromal cells; Tissue-specific stem cells