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 MeshorerEmail author


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.


Progerin iPS cells iPSC Neuronal differentiation Embryonic stem cells HD 


Author Contributions

D. Cohen-Carmon, M. Sorek, V. Lerner, Y. Yarom, and E. Meshorer designed the research; D. Cohen-Carmon, M. Sorek, V. Lerner, and M. Nissim-Rafinia performed the research; D. Cohen-Carmon, M. Sorek, and V. Lerner analyzed the data; Cohen-Carmon, M. Sorek, and E. Meshorer wrote the paper.

Funding Information

The work was supported by the Israel Science Foundation (1140/17 to E.M.), a TEVA National Network of Excellence award (to E.M. and D.C.C), and the Azrieli Foundation Fellowship (to M.S.).

Supplementary material

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Copyright information

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

Authors and Affiliations

  1. 1.Department of Genetics, The Alexander Silberman Institute of Life Sciences, Edmond J. Safra CampusThe Hebrew University of JerusalemJerusalemIsrael
  2. 2.The Edmond and Lily Safra Center for Brain Sciences, Edmond J. Safra CampusThe Hebrew University of JerusalemJerusalemIsrael
  3. 3.Department of Neurobiology, The Alexander Silberman Institute of Life Sciences, Edmond J. Safra CampusThe Hebrew University of JerusalemJerusalemIsrael
  4. 4.Department of PathologySree Chitra Tirunal Institute for Medical Sciences and TechnologyThiruvananthapuramIndia

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