title: Salivary gland homeostasis is maintained through acinar cell self-duplication.
abstract: Current dogma suggests that salivary gland homeostasis is stem cell dependent. However, the extent of stem cell contribution to salivary gland maintenance has not been determined. We investigated acinar cell replacement during homeostasis, growth, and regeneration, using an inducible CreER(T2) expressed under the control of the Mist1 gene locus. Genetic labeling, followed by a chase period, showed that acinar cell replacement is not driven by the differentiation of unlabeled stem cells. Analysis using R26(Brainbow2.1) reporter revealed continued proliferation and clonal expansion of terminally differentiated acinar cells in all major salivary glands. Induced injury also demonstrated the regenerative potential of pre-labeled acinar cells. Our results support a revised model for salivary gland homeostasis based predominantly on self-duplication of acinar cells, rather than on differentiation of stem cells. The proliferative capacity of differentiated acinar cells may prove critical in the implementation of cell-based strategies to restore the salivary glands.
authors.affiliation: Center for Oral Biology, Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Marit H
authors.initials: MH
authors.lastname: Aure
authors.affiliation: Department of Biological Sciences, Purdue Center for Cancer Research, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Konieczny
authors.affiliation: Center for Oral Biology, Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. Electronic address: catherine_ovitt@urmc.rochester.edu.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Ovitt
mesh_terms: D061354:Acinar Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012469:Salivary Glands / Q000166:cytology* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C491312:Bhlha15 protein, mouse
references.citation: Crit Rev Oral Biol Med. 1993;4(5):639-77
references.pmid: 8292713
references.citation: Anat Rec. 1993 Mar;235(3):475-85
references.pmid: 8430917
references.citation: Anat Rec. 1999 Mar;254(3):408-17
references.pmid: 10096673
references.citation: Anat Rec. 1999 Sep 1;256(1):84-90
references.pmid: 10456989
references.citation: Braz Oral Res. 2006 Jan-Mar;20(1):13-20
references.pmid: 16729169
references.citation: Tissue Eng. 2007 Apr;13(4):721-35
references.pmid: 17341161
references.citation: Dev Cell. 2007 May;12(5):817-26
references.pmid: 17488631
references.citation: Semin Cell Dev Biol. 2007 Apr;18(2):237-44
references.pmid: 17336109
references.citation: Anat Rec. 2000 Jun 1;259(2):157-67
references.pmid: 10820318
references.citation: J Cell Physiol. 2000 Mar;182(3):311-22
references.pmid: 10653597
references.citation: Dev Biol. 2008 Aug 1;320(1):72-8
references.pmid: 18572159
references.citation: Anat Rec. 2001 Jun 1;263(2):202-14
references.pmid: 11360236
references.citation: Arch Oral Biol. 2001 Oct;46(10):909-18
references.pmid: 11451405
references.citation: Dev Biol. 2001 Dec 15;240(2):517-30
references.pmid: 11784080
references.citation: J Histochem Cytochem. 2009 Apr;57(4):383-96
references.pmid: 19110483
references.citation: Gastroenterology. 2009 Apr;136(4):1368-78
references.pmid: 19249398
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7101-6
references.pmid: 19372370
references.citation: Front Oral Biol. 2010;14:90-106
references.pmid: 20428013
references.citation: Science. 2010 Sep 24;329(5999):1645-7
references.pmid: 20929848
references.citation: Int J Radiat Oncol Biol Phys. 2010 Nov 15;78(4):983-91
references.pmid: 20970030
references.citation: Cell Stem Cell. 2011 Oct 4;9(4):317-29
references.pmid: 21982232
references.citation: Stem Cells. 2013 Apr;31(4):613-9
references.pmid: 23335219
references.citation: Nat Commun. 2013;4:2498
references.pmid: 24084982
references.citation: Stem Cell Reports. 2013;1(6):604-19
references.pmid: 24371813
references.citation: Cell Stem Cell. 2014 Sep 4;15(3):340-9
references.pmid: 25130492
references.citation: J Neurosci Methods. 2002 Mar 30;115(1):97-105
references.pmid: 11897369
references.citation: Nature. 2004 May 6;429(6987):41-6
references.pmid: 15129273
references.citation: J Cell Biol. 1970 Jul;46(1):81-7
references.pmid: 5459013
references.citation: J Ultrastruct Res. 1971 Feb;34(3):276-87
references.pmid: 4926049
references.citation: Cell Tissue Kinet. 1982 Mar;15(2):187-95
references.pmid: 7066959
references.citation: Anat Rec. 1985 Oct;213(2):150-8
references.pmid: 4073568
references.citation: J Anat. 1988 Dec;161:143-51
references.pmid: 3254887
references.citation: J Anat. 1990 Oct;172:115-27
references.pmid: 2272897
references.citation: Dev Biol. 1997 Feb 1;182(1):101-13
references.pmid: 9073453