title: Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium.
abstract: Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs.
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111; Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111; Medical Scientist Training Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111;
authors: Nikolai
authors: N
authors: Schnittke
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111; Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111; Medical Scientist Training Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111;
authors: Daniel B
authors: DB
authors: Herrick
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111; Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111;
authors: Brian
authors: http://orcid.org/0000-0002-8851-3534
authors: B
authors: Lin
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111; Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111;
authors: Jesse
authors: J
authors: Peterson
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111; Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111.
authors: Julie H
authors: JH
authors: Coleman
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111; Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111;
authors: Adam I
authors: AI
authors: Packard
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111;
authors: Woochan
authors: W
authors: Jang
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111; jim.schwob@tufts.edu.
authors: James E
authors: JE
authors: Schwob
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000235:genetics; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse
keywords: colony-forming unit; lineage tracing; neural regeneration; reserve stem cell; retroviral transduction