title: Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor.
abstract: Mesenchymal stem cells (MSCs) are typically defined by their in vitro characteristics, and as a consequence the in vivo identity of MSCs and their niches are poorly understood. To address this issue, we used lineage tracing in a mouse incisor model and identified the neurovascular bundle (NVB) as an MSC niche. We found that NVB sensory nerves secrete Shh protein, which activates Gli1 expression in periarterial cells that contribute to all mesenchymal derivatives. These periarterial cells do not express classical MSC markers used to define MSCs in vitro. In contrast, NG2(+) pericytes represent an MSC subpopulation derived from Gli1+ cells; they express classical MSC markers and contribute little to homeostasis but are actively involved in injury repair. Likewise, incisor Gli1(+) cells, but not NG2(+) cells, exhibit typical MSC characteristics in vitro. Collectively, we demonstrate that MSCs originate from periarterial cells and are regulated by Shh secretion from an NVB.
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, Los Angeles, CA 90033, USA.
authors: Hu
authors: H
authors: Zhao
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, Los Angeles, CA 90033, USA.
authors: Jifan
authors: J
authors: Feng
authors: Department of Orofacial Sciences and Pediatrics, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
authors: Kerstin
authors: K
authors: Seidel
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, Los Angeles, CA 90033, USA.
authors: Songtao
authors: S
authors: Shi
authors: Department of Orofacial Sciences and Pediatrics, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
authors: Ophir
authors: O
authors: Klein
authors: Department of Craniofacial Development and Stem Cell Biology, Dental Institute, Kings College London, London TN3 9TF, UK.
authors: Paul
authors: P
authors: Sharpe
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, Los Angeles, CA 90033, USA. Electronic address: ychai@usc.edu.
authors: Yang
authors: Y
authors: Chai
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001158:Arteries / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D006168:Guinea Pigs; D053823:Hedgehog Proteins / Q000378:metabolism*; D006706:Homeostasis; D007180:Incisor / Q000098:blood supply / Q000166:cytology* / Q000294:innervation*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D013194:Staining and Labeling; D055153:Stem Cell Niche; D000071676:Zinc Finger Protein GLI1; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D015415:Biomarkers; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D011509:Proteoglycans; D000071676:Zinc Finger Protein GLI1; D000099216:Chondroitin Sulfate Proteoglycan 4; C498520:Gli1 protein, mouse; C465570:Shh protein, mouse