title: Differentiation potential of individual olfactory c-Kit+ progenitors determined via multicolor lineage tracing.
abstract: Olfactory tissue undergoes lifelong renewal, due to the presence of basal neural stem cells. Multiple categories of globose basal stem cells have been identified, expressing markers such as Lgr5, Ascl1, GBC-2, and c-Kit. The differentiation potential of individual globose cells has remained unclear. Here, we utilized Cre/loxP lineage tracing with a multicolor reporter system to define c-Kit+ cell contributions at clonal resolution. We determined that reporter expression permitted identification of c-Kit derived progeny with fine cellular detail, and that clones were found to be comprised by neurons only, microvillar cells only, microvillar cells and neurons, or gland/duct cells. Quantification of reporter-labeled cells indicated that c-Kit+ cells behave as transit amplifying or immediate precursors, although we also found evidence for longer-term c-Kit+ cell contributions. Our results from the application of multicolor fate mapping delineate the clonal contributions of c-Kit+ cells to olfactory epithelial renewal, and provide novel insight into tissue maintenance of an adult neuroepithelium.
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Goss
authors.affiliation: Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Nirupa
authors.initials: N
authors.lastname: Chaudhari
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Raphael
authors.initials: R
authors.lastname: Nwojo
authors.affiliation: Department of Internal Medicine, Technical University of Munich, München, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Seidler
authors.affiliation: Department of Internal Medicine, Technical University of Munich, München, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.|Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D058953:Neural Stem Cells / Q000166:cytology*; D009831:Olfactory Mucosa / Q000166:cytology*; D018034:Olfactory Receptor Neurons / Q000166:cytology*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: neurogenesis; olfaction; receptor tyrosine kinase; regeneration; stem cells