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Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.

Publication ,  Journal Article
Goldstein, BJ; Goss, GM; Hatzistergos, KE; Rangel, EB; Seidler, B; Saur, D; Hare, JM
Published in: J Comp Neurol
January 1, 2015

The olfactory epithelium houses chemosensory neurons, which transmit odor information from the nose to the brain. In adult mammals, the olfactory epithelium is a uniquely robust neuroproliferative zone, with the ability to replenish its neuronal and non-neuronal populations due to the presence of germinal basal cells. The stem and progenitor cells of these germinal layers, and their regulatory mechanisms, remain incompletely defined. Here we show that progenitor cells expressing c-Kit, a receptor tyrosine kinase marking stem cells in a variety of embryonic tissues, are required for maintenance of the adult neuroepithelium. Mouse genetic fate-mapping analyses show that embryonically, a c-Kit(+) population contributes to olfactory neurogenesis. In adults under conditions of normal turnover, there is relatively sparse c-Kit(+) progenitor cell (ckPC) activity. However, after experimentally induced neuroepithelial injury, ckPCs are activated such that they reconstitute the neuronal population. There are also occasional non-neuronal cells found to arise from ckPCs. Moreover, the selective depletion of the ckPC population, utilizing temporally controlled targeted diphtheria toxin A expression, results in failure of neurogenesis after experimental injury. Analysis of this model indicates that most ckPCs reside among the globose basal cell populations and act downstream of horizontal basal cells, which can serve as stem cells. Identification of the requirement for olfactory c-Kit-expressing progenitors in olfactory maintenance provides new insight into the mechanisms involved in adult olfactory neurogenesis. Additionally, we define an important and previously unrecognized site of adult c-Kit activity.

Duke Scholars

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Published In

J Comp Neurol

DOI

EISSN

1096-9861

Publication Date

January 1, 2015

Volume

523

Issue

1

Start / End Page

15 / 31

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-kit
  • Olfactory Receptor Neurons
  • Olfactory Mucosa
  • Neurology & Neurosurgery
  • Neurogenesis
  • Neural Stem Cells
  • Nerve Regeneration
  • Microscopy, Confocal
  • Mice, Transgenic
  • Mice, Inbred C57BL
 

Citation

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Goldstein, B. J., Goss, G. M., Hatzistergos, K. E., Rangel, E. B., Seidler, B., Saur, D., & Hare, J. M. (2015). Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons. J Comp Neurol, 523(1), 15–31. https://doi.org/10.1002/cne.23653
Goldstein, Bradley J., Garrett M. Goss, Konstantinos E. Hatzistergos, Erika B. Rangel, Barbara Seidler, Dieter Saur, and Joshua M. Hare. “Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.J Comp Neurol 523, no. 1 (January 1, 2015): 15–31. https://doi.org/10.1002/cne.23653.
Goldstein BJ, Goss GM, Hatzistergos KE, Rangel EB, Seidler B, Saur D, et al. Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons. J Comp Neurol. 2015 Jan 1;523(1):15–31.
Goldstein, Bradley J., et al. “Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.J Comp Neurol, vol. 523, no. 1, Jan. 2015, pp. 15–31. Pubmed, doi:10.1002/cne.23653.
Goldstein BJ, Goss GM, Hatzistergos KE, Rangel EB, Seidler B, Saur D, Hare JM. Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons. J Comp Neurol. 2015 Jan 1;523(1):15–31.
Journal cover image

Published In

J Comp Neurol

DOI

EISSN

1096-9861

Publication Date

January 1, 2015

Volume

523

Issue

1

Start / End Page

15 / 31

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-kit
  • Olfactory Receptor Neurons
  • Olfactory Mucosa
  • Neurology & Neurosurgery
  • Neurogenesis
  • Neural Stem Cells
  • Nerve Regeneration
  • Microscopy, Confocal
  • Mice, Transgenic
  • Mice, Inbred C57BL