Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Goldstein, BJ; Goss, GM; Choi, R; Saur, D; Seidler, B; Hare, JM; Chaudhari, N

Published Date

  • December 1, 2016

Published In

Volume / Issue

  • 143 / 23

Start / End Page

  • 4394 - 4404

PubMed ID

  • 27789621

Pubmed Central ID

  • 27789621

Electronic International Standard Serial Number (EISSN)

  • 1477-9129

Digital Object Identifier (DOI)

  • 10.1242/dev.142653

Language

  • eng

Conference Location

  • England