Author:
Gracia-Diaz Carolina,Perdomo Jonathan E.,Khan Munir E.,Disanza Brianna,Cajka Gregory G.,Lei Sunyimeng,Gagne Alyssa,Maguire Jean Ann,Roule Thomas,Shalem Ophir,Bhoj Elizabeth J.,Ahrens-Nicklas Rebecca C.,French Deborah,Goldberg Ethan M.,Wang Kai,Glessner Joseph,Akizu Naiara
Abstract
SummaryThe KOLF2.1J iPSC line was recently proposed as a reference iPSC to promote the standardization of research studies in the stem cell field. Due to overall good performance differentiating to neural cell lineages, high gene editing efficiency, and absence of genetic variants associated to neurological disorders KOLF2.1J iPSC line was particularly recommended for neurodegenerative disease modeling. However, our work uncovers that KOLF2.1J hPSCs carry heterozygous small copy number variants (CNVs) that causeDTNBP1, JARID2andASTN2haploinsufficiencies, all of which are associated with neurological disorders. We further determine that these CNVs arosein vitroover the course of KOLF2.1J iPSC generation from a healthy donor-derived KOLF2 iPSC line and affect the expression of DNTBP1, JARID2 and ASTN2 proteins in KOLF2.1J iPSCs and neural progenitors. Therefore, our study suggests that KOLF2.1J iPSCs carry genetic variants that may be deleterious for neural cell lineages. This data is essential for a careful interpretation of neural cell studies derived from KOLF2.1J iPSCs and highlights the need for a catalogue of iPSC lines that includes a comprehensive genome characterization analysis.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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