Human Induced Pluripotent Stem Cell-Based Modelling of Spinocerebellar Ataxias

Stem Cell Rev Rep. 2022 Feb;18(2):441-456. doi: 10.1007/s12015-021-10184-0. Epub 2021 May 25.


Dominant spinocerebellar ataxias (SCAs) constitute a large group of phenotypically and genetically heterogeneous disorders that mainly present with dysfunction of the cerebellum as their main hallmark. Although animal and cell models have been highly instrumental for our current insight into the underlying disease mechanisms of these neurodegenerative disorders, they do not offer the full human genetic and physiological context. The advent of human induced pluripotent stem cells (hiPSCs) and protocols to differentiate these into essentially every cell type allows us to closely model SCAs in a human context. In this review, we systematically summarize recent findings from studies using hiPSC-based modelling of SCAs, and discuss what knowledge has been gained from these studies. We conclude that hiPSC-based models are a powerful tool for modelling SCAs as they contributed to new mechanistic insights and have the potential to serve the development of genetic therapies. However, the use of standardized methods and multiple clones of isogenic lines are essential to increase validity and reproducibility of the insights gained.

Keywords: Ataxia; Cerebellum; Disease modelling; Induced pluripotent stem cells; Neurons; Spinocerebellar ataxia.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum
  • Genetic Therapy
  • Humans
  • Induced Pluripotent Stem Cells*
  • Reproducibility of Results
  • Spinocerebellar Ataxias* / genetics
  • Spinocerebellar Ataxias* / therapy