Primary proprioceptive neurons from human induced pluripotent stem cells: a cell model for afferent ataxias

Human induced pluripotent stem cells (iPSCs) are used to generate models of human diseases that recapitulate the pathogenic process as it occurs in affected cells. Many differentiated cell types can currently be obtained from iPSCs, but no validated protocol is yet available to specifically generate...

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Bibliographic Details
Published in:Scientific reports 2020-05, Vol.10 (1), p.7752, Article 7752
Main Authors: Dionisi, Chiara, Rai, Myriam, Chazalon, Marine, Schiffmann, Serge N., Pandolfo, Massimo
Format: Article
Language:English
Subjects:
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Ataxia
Cell Differentiation
Dorsal root ganglia
Flow cytometry
Friedreich Ataxia - pathology
Friedreich's ataxia
Humanities and Social Sciences
Humans
Induced Pluripotent Stem Cells - pathology
Inhibitory postsynaptic potentials
multidisciplinary
Neurogenesis
Neurons
Pluripotency
Proprioception
Proprioceptors
Science
Science (multidisciplinary)
Sensory neurons
Sensory Receptor Cells - pathology
Smad protein
Stem cells
Wnt protein
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Summary:Human induced pluripotent stem cells (iPSCs) are used to generate models of human diseases that recapitulate the pathogenic process as it occurs in affected cells. Many differentiated cell types can currently be obtained from iPSCs, but no validated protocol is yet available to specifically generate primary proprioceptive neurons. Proprioceptors are affected in a number of genetic and acquired diseases, including Friedreich ataxia (FRDA). To develop a cell model that can be applied to conditions primarily affecting proprioceptors, we set up a protocol to differentiate iPSCs into primary proprioceptive neurons. We modified the dual-SMAD inhibition/WNT activation protocol, previously used to generate nociceptor-enriched cultures of primary sensory neurons from iPSCs, to favor instead the generation of proprioceptors. We succeeded in substantially enriching iPSC-derived primary sensory neuron cultures for proprioceptors, up to 50% of finally differentiated neurons, largely exceeding the proportion of 7.5% normally represented by these cells in dorsal root ganglia. We also showed that almost pure populations of proprioceptors can be purified from these cultures by fluorescence-activated cell sorting. Finally, we demonstrated that the protocol can be used to generate proprioceptors from iPSCs from FRDA patients, providing a cell model for this genetic sensory neuronopathy.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-64831-6