Samuel P Gubbels, MD

Slide of the Week: Samuel P Gubbels, MD

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

Legend: Left image: Cochlea from an adult nestin-CreERT2/tdTomato-reporter mouse 56 days post tamoxifen injection. Low power macroscopic imaging analysis showed a pattern of tdTomato expression on the neural aspect of Sox2-positive supporting cells. An apical-basal gradient was not observed in tdTomato-positive cells. Image was acquired on a Lightsheet Z.1 by Carl Zeiss Microscopy GmbH with a 5x/0.16 EC Plan-NEOFLUAR objective. Scale bar: 500µm.  Right image: Apical region of the cochlea 7 days after the last tamoxifen injection. TdTomato-positive cells are located below and medial to the inner hair cell layer and co-localize with the stem cell and supporting cell marker Sox2. Scale bar: 10 µm.

Citation: Chow CL, Guo W, Trivedi P, Zhao X, Gubbels SP. (2015) Characterization of a unique cell population marked by transgene expression in the adult cochlea of nestin-CreER(T2)/tdTomato-reporter mice. The Journal of Comparative Neurology. 523(10):1474-87. doi: 10.1002/cne.23747.

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.

About the investigator: Samuel Gubbels, MD, FACS, is a Waisman Center investigator and assistant professor in the Department of Surgery, Division of Otolaryngology-Head and Neck Surgery at UW-Madison. His clinical practice is devoted to the treatment of adults and children with hearing loss and ear disease, with particular focus on cochlear implantation. His research interests are in the development of novel methods to study and treat hearing loss using different types of stem cells to generate the hair cells of the inner ear.

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