Title: Direct reprogramming of canine fibroblasts to induced-motor neurons: A model for age-related canine peripheral neuropathies
Abstract: Spontaneous, heritable, late-onset peripheral neuropathies are common and life-limiting in the canine pet population. These conditions are strong potential models for similar human conditions, such as Charcot-Marie-Tooth disease. Investigation into these conditions is limited by a lack of a subtype-specific neuronal culture model that accurately recapitulates an aged phenotype in dogs. Direct reprogramming is a method through which a cell’s fate can be converted, while maintaining biological age. In this study, we developed a direct reprogramming method that utilizes transcription factors and small molecules to generate induced-motor neurons (iMNs) from canine primary dermal fibroblasts. Reprogrammed iMNs from dogs of a variety of ages are electrically active and express early and late protein markers of bona fide motor neuron such as HB9, TUBB3, ChAT, and MAP2. When plated on mouse astrocyte cultures for long-term maintenance, iMNs develop sophisticated neurites that can be used to study features of axonal degeneration in vitro. IMN cultures from dogs affected with a late-onset peripheral neuropathy have been recently developed to investigate cellular and molecular features of the disease. These studies are ongoing. The development of this direct reprogramming model offers new possibilities for studying age-related canine neurodegenerative diseases, allowing for a deeper understanding of disease mechanisms and potential therapeutic strategies in these valuable dog models.
Our Seminar Lab Series will be offered in hybrid format:
The in-person seminar is each Tuesday during the semester from noon-1 p.m. at the Discovery Building, DeLuca Forum.
To join online, please click the zoom link below:
https://uwmadison.zoom.us/j/96958883460
*if you are asked for a passcode: 970506