iPSC Neurodegenerative Disease Initiative isogenic CAG repeat iPSC line for Huntingtons disease

Salazar, L.; Burns, M. S.; Stocksdale, J. T.; Wang, K. Q.; Cao, G.; Miramontes, R.; McClure, N. R.; Ho, L.; Keith, A. R.; Sutherland, M.; Cookson, M. R.; Ward, M.; Skarnes, W. C.; Thompson, L. M.

doi:10.64898/2026.06.30.735662

bioRxiv · 10.64898/2026.06.30.735662

iPSC Neurodegenerative Disease Initiative isogenic CAG repeat iPSC line for Huntingtons disease

Salazar, L.·Burns, M. S.·Stocksdale, J. T.·Wang, K. Q.·Cao, G.·Miramontes, R.·McClure, N. R.·Ho, L.·Keith, A. R.·Sutherland, M.·Cookson, M. R.·Ward, M.·Skarnes, W. C.·Thompson, L. M.

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Abstract

STRUCTURED ABSTRACTO_ST_ABSPurpose of ResearchC_ST_ABSThe generation of iPSC lines expressing 21, 56 and 79 glutamine repeats within the HTT protein and homozygous KO of HTT in the KOLF2.1J background as an additional disease series within the iPSC Neurodegenerative Disease Initiative (iNDI) collection. Major FindingsAll iPSCs, even those expressing long repeats of 79Q or HTT KO, were capable of differentiating to striatal and cortical neurons, astrocytes and microglia using established protocols. General quality control stains and morphological analyses are described for each differentiation. A selected set of assays were carried out on differentiated cells; expanded repeat expressing astrocytes showed altered expression of astrocyte protein markers and morphological characteristics, and striatal neurons showed altered DARPP-32/CTIP2 colocalization. mRNAseq carried out for striatal neurons showed high similarities in gene expression changes between 79Q and KO lines compared to the unexpanded repeat. ConclusionsThe KOLF2.1J isogenic CAG repeat series serves as a community resource to study HD mechanisms with the potential for direct comparison across other neurodegenerative diseases through the iNDI collection.

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Salazar, L., Burns, M. S., Stocksdale, J. T., Wang, K. Q., Cao, G., Miramontes, R., McClure, N. R., Ho, L., Keith, A. R., Sutherland, M., Cookson, M. R., Ward, M., Skarnes, W. C., Thompson, L. M.. 2026-07-04. iPSC Neurodegenerative Disease Initiative isogenic CAG repeat iPSC line for Huntingtons disease. https://doi.org/10.64898/2026.06.30.735662

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