Characterization of a unique cell population marked by transgene expression in the adult cochlea of nestin-CreER(T2)/tdTomato-reporter mice

J Comp Neurol. 2015 Jul 1;523(10):1474-87. doi: 10.1002/cne.23747. Epub 2015 Mar 10.

Abstract

Hair cells in the adult mammalian cochlea cannot spontaneously regenerate after damage, resulting in the permanency of hearing loss. Stem cells have been found to be present in the cochlea of young rodents; however, there has been little evidence for their existence into adulthood. We used nestin-CreER(T2)/tdTomato-reporter mice to trace the lineage of putative nestin-expressing cells and their progeny in the cochleae of adult mice. Nestin, an intermediate filament found in neural progenitor cells during early development and adulthood, is regarded as a multipotent and neural stem cell marker. Other investigators have reported its presence in postnatal and young adult rodents; however, there are discrepancies among these reports. Using lineage tracing, we documented a robust population of tdTomato-expressing cells and evaluated these cells at a series of adult time points. Upon activation of the nestin promoter, tdTomato was observed just below and medial to the inner hair cell layer. All cells colocalized with the stem cell and cochlear-supporting-cell marker Sox2 as well as the supporting cell and Schwann cell marker Sox10; however, they did not colocalize with the Schwann cell marker Krox20, spiral ganglion marker NF200, nor glial fibrillary acidic acid (GFAP)-expressing supporting cell marker. The cellular identity of this unique population of tdTomato-expressing cells in the adult cochlea of nestin-CreER(T2)/tdTomato mice remains unclear; however, these cells may represent a type of supporting cell on the neural aspect of the inner hair cell layer.

Keywords: AB_10013382; AB_10015251; AB_10064079; AB_149792; AB_2195374; AB_2251134; AB_2286684; AB_2314882; AB_306298; AB_396354; inner ear; mouse; regeneration; stem cell; supporting cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Cochlea / cytology*
  • Ear, Inner / metabolism
  • Estrogen Antagonists / pharmacology
  • Etoposide
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Ifosfamide
  • Ki-67 Antigen / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Methotrexate
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nestin / genetics
  • Nestin / metabolism*
  • Neurons / classification*
  • Neurons / metabolism*
  • Plant Lectins / genetics
  • Plant Lectins / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Tamoxifen / pharmacology

Substances

  • Estrogen Antagonists
  • Ki-67 Antigen
  • Luminescent Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Nestin
  • Plant Lectins
  • Receptors, Estrogen
  • tomato lectin
  • Tamoxifen
  • Etoposide
  • Ifosfamide
  • Methotrexate

Supplementary concepts

  • IMVP-16 protocol