title: Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo.
abstract: Olfactory epithelium (OE) has a lifelong capacity for neurogenesis due to the presence of basal stem cells. Despite the ability to generate short-term cultures, the successful in vitro expansion of purified stem cells from adult OE has not been reported. We sought to establish expansion-competent OE stem cell cultures to facilitate further study of the mechanisms and cell populations important in OE renewal. Successful cultures were prepared using adult mouse basal cells selected for expression of c-KIT. We show that c-KIT signaling regulates self-renewal capacity and prevents neurodifferentiation in culture. Inhibition of TGFβ family signaling, a known negative regulator of embryonic basal cells, is also necessary for maintenance of the proliferative, undifferentiated state in vitro Characterizing successful cultures, we identified expression of BMI1 and other Polycomb proteins not previously identified in olfactory basal cells but known to be essential for self-renewal in other stem cell populations. Inducible fate mapping demonstrates that BMI1 is expressed in vivo by multipotent OE progenitors, validating our culture model. These findings provide mechanistic insights into the renewal and potency of olfactory stem cells.
authors: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA b.goldstein4@med.miami.edu.|Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|Program in Neurosciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Bradley J
authors: 0000-0002-9612-1696
authors: BJ
authors: Goldstein
authors: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Garrett M
authors: GM
authors: Goss
authors: MD, PhD Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Rhea
authors: R
authors: Choi
authors: Department of Internal Medicine, Technical University of Munich, 80333 Munich, Germany.
authors: Dieter
authors: D
authors: Saur
authors: Department of Internal Medicine, Technical University of Munich, 80333 Munich, Germany.
authors: Barbara
authors: B
authors: Seidler
authors: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Joshua M
authors: JM
authors: Hare
authors: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|Program in Neurosciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Nirupa
authors: N
authors: Chaudhari
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation / Q000502:physiology; D000066673:Cell Self Renewal / Q000502:physiology*; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D009831:Olfactory Mucosa / Q000166:cytology*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: C489421:Bmi1 protein, mouse; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D063150:Polycomb Repressive Complex 1; D019009:Proto-Oncogene Proteins c-kit
keywords: BMI1; KIT; Neurogenesis; Olfaction; Stem cells