iPSC neurodegenerative disease initiative isogenic CAG repeat iPSC line for Huntington’s disease

16/10/2026

AI Summary

Generation of isogenic KOLF2.1J iPSC lines with HTT CAG repeats 21, 56, 79 and homozygous KO as iNDI resource.
All lines differentiate into striatal and cortical neurons, astrocytes and microglia; 79Q and KO show astrocyte marker and morphology alterations.
mRNAseq revealed similar gene expression changes in 79Q and KO striatal neurons versus unexpanded repeat, supporting comparative HD mechanism studies.

TL;DR (AI Generated)

J Huntingtons Dis. 2026 Oct 16:18796397261497434. doi: 10.1177/18796397261497434.

Purpose of ResearchThe 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.

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.

Basic summary

J Huntingtons Dis. 2026 Oct 16:18796397261497434. doi: 10.1177/18796397261497434. Online ahead of print.

ABSTRACT

Purpose of ResearchThe 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.

PMID:42885744 | DOI:10.1177/18796397261497434

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