Conversion of Mouse and Human Fibroblasts into Functional Spinal Motor Neurons
By Esther Y. Son, J. Ichida, Brian J. Wainger, Jeremy S. Toma, V. Rafuse, Clifford J. Woolf, K. Eggan. Cell Stem Cell, 2011
669 citations recorded by the source corpus.
SUMMARY The mammalian nervous system is composed of a multitude of distinct neuronal subtypes, each with its own phenotype and differential sensitivity to degenerative disease. Although specific neuronal types can be isolated from rodent embryos or engineered from stem cells for translational studies, transcription factor mediated reprogramming might provide a more direct route to their generation. Here we report that the forced expression of select transcription factors is sufficient to convert mouse and human fibroblasts into induced motor neurons (iMNs). iMNs displayed a morphology, gene expression signature, electrophysiology, synaptic functionality, in vivo engraftment capacity and sensitivity to degenerative stimuli, similar to embryo-derived motor neurons. We show that the converting fibroblasts do not transit through a proliferative neural progenitor state, and thus form bona fide motor neurons via a route distinct from embryonic development. Our findings demonstrate that fibroblasts can be converted directly into a specific differentiated and functional neural subtype, the spinal motor neuron.
Subfields: Developmental Neuroscience, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/c3f8a63079097af891c08b2f2a5c83d3af513b2f
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Citations in the corpus
- Generation of functional human pancreatic β cells in vitro (2014, background): “Recent research has moved the stem cell field closer to that goal through development of strategies to generate cells that would otherwise be difficult to obtain, like neurons or cardiomyocytes (Kriks et al., 2011; Shiba et al., 2012; Son et al., 2011).”
- In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model (2013, background): “Many studies have since demonstrated transdifferentiation across different cell lineages, including reprogramming mouse or human fibroblasts directly into neurons (Ambasudhan et al., 2011; Caiazzo et al., 2011; Kim et al., 2011; Ladewig et al., 2012; Liu et al., 2012, 2013; Meng et al., 2012; Pang e”