title: Glial origin of mesenchymal stem cells in a tooth model system.
abstract: Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium. It has been thought for decades that the dental mesenchymal stem cells giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue. Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.
authors: 1] Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden [2].
authors: Nina
authors: N
authors: Kaukua
authors: 1] Department of Dental Medicine, Karolinska Institutet, Stockholm 17177, Sweden [2].
authors: Maryam Khatibi
authors: MK
authors: Shahidi
authors: Division of Molecular Neurobiology, MRC National Institute for Medical Research, London NW7 1AA, UK.
authors: Chrysoula
authors: C
authors: Konstantinidou
authors: 1] Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden [2] A.V. Zhirmunsky Institute of Marine Biology of the Far Eastern Branch of the Russian Academy of Sciences, Vladivostok 690041, Russia.
authors: Vyacheslav
authors: V
authors: Dyachuk
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden.
authors: Marketa
authors: M
authors: Kaucka
authors: Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden.
authors: Alessandro
authors: A
authors: Furlan
authors: Department of Craniofacial Development and Stem Cell Biology, King's College London Dental Institute, Guy's Hospital, London SE1 3QD, UK.
authors: Zhengwen
authors: Z
authors: An
authors: Department of Craniofacial Development and Stem Cell Biology, King's College London Dental Institute, Guy's Hospital, London SE1 3QD, UK.
authors: Longlong
authors: L
authors: Wang
authors: Department of Women's and Children's Health, Karolinska Institutet, Stockholm 17177, Sweden.
authors: Isabell
authors: I
authors: Hultman
authors: Department of Women's and Children's Health, Karolinska Institutet, Stockholm 17177, Sweden.
authors: Lars
authors: L
authors: Ahrlund-Richter
authors: Science for Life Laboratory, Royal Institute of Technology, Stockholm 17177, Sweden.
authors: Hans
authors: H
authors: Blom
authors: Science for Life Laboratory, Royal Institute of Technology, Stockholm 17177, Sweden.
authors: Hjalmar
authors: H
authors: Brismar
authors: Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden.
authors: Natalia Assaife
authors: NA
authors: Lopes
authors: Division of Molecular Neurobiology, MRC National Institute for Medical Research, London NW7 1AA, UK.
authors: Vassilis
authors: V
authors: Pachnis
authors: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich CH-8093, Switzerland.
authors: Ueli
authors: U
authors: Suter
authors: 1] Hubrecht Institute, Koninklijke Nederlandse Akademie van Wetenschappen (KNAW), PO Box 85164, 3508 AD Utrecht, the Netherlands [2] Department of Molecular Genetics, University Medical Center Utrecht, Utrecht 3508 GA, the Netherlands.
authors: Hans
authors: H
authors: Clevers
authors: Institute of Biotechnology, Developmental Biology Program, University of Helsinki, Helsinki FI-00014, Finland.
authors: Irma
authors: I
authors: Thesleff
authors: Department of Craniofacial Development and Stem Cell Biology, King's College London Dental Institute, Guy's Hospital, London SE1 3QD, UK.
authors: Paul
authors: P
authors: Sharpe
authors: Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden.
authors: Patrik
authors: P
authors: Ernfors
authors: Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden.
authors: Kaj
authors: K
authors: Fried
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden.
authors: Igor
authors: I
authors: Adameyko
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D058948:Cell Tracking; D002999:Clone Cells / Q000166:cytology; D003782:Dental Pulp / Q000166:cytology; D005260:Female; D007180:Incisor / Q000166:cytology* / Q000196:embryology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008954:Models, Biological; D009432:Neural Crest / Q000166:cytology; D009457:Neuroglia / Q000166:cytology*; D009804:Odontoblasts / Q000166:cytology; D012038:Regeneration; D012583:Schwann Cells / Q000166:cytology