Progerin-Induced Transcriptional Changes in Huntington’s Disease Human Pluripotent Stem Cell-Derived Neurons

Dorit Cohen-Carmon, Matan Sorek, Vitaly Lerner, Mundackal S. Divya, Malka Nissim-Rafinia, Yosef Yarom, Eran Meshorer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Huntington’s disease (HD) is a neurodegenerative late-onset genetic disorder caused by CAG expansions in the coding region of the Huntingtin (HTT) gene, resulting in a poly-glutamine (polyQ) expanded HTT protein. Considerable efforts have been devoted for studying HD and other polyQ diseases using animal models and cell culture systems, but no treatment currently exists. Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) offer an elegant solution for modeling human diseases. However, as embryonic or rejuvenated cells, respectively, these pluripotent stem cells (PSCs) do not recapitulate the late-onset feature of the disease. Here, we applied a robust and rapid differentiation protocol to derive electrophysiologically active striatal GABAergic neurons from human wild-type (WT) and HD ESCs and iPSCs. RNA-seq analyses revealed that HD and WT PSC-derived neurons are highly similar in their gene expression patterns. Interestingly, ectopic expression of Progerin in both WT and HD neurons exacerbated the otherwise non-significant changes in gene expression between these cells, revealing IGF1 and genes involved in neurogenesis and nervous system development as consistently altered in the HD cells. This work provides a useful tool for modeling HD in human PSCs and reveals potential molecular targets altered in HD neurons.

Original languageAmerican English
Pages (from-to)1768-1777
Number of pages10
JournalMolecular Neurobiology
Issue number3
StatePublished - 1 Mar 2020

Bibliographical note

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© 2020, Springer Science+Business Media, LLC, part of Springer Nature.


  • Embryonic stem cells
  • HD
  • Neuronal differentiation
  • Progerin
  • iPS cells
  • iPSC


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