Syndromic RNA polymerase II insufficiency: Generation of a human induced pluripotent stem cell line (UUIGPi002A-5) with a heterozygous disruption of POLR2A.

Schuster J, de Guidi C, Fatima A, Sobol M, Dahl N

Stem Cell Res 57 (-) 102577 [2021-12-00; online 2021-10-19]

Heterozygous variants in POLR2A, encoding the largest subunit of RNA polymerase II, cause severe neurodevelopmental and multisystem abnormalities in humans. Using CRISPR/Cas9 we generated the human iPSC line KICRi002A-5 with a heterozygous truncating 4 bp insertion in exon 5 of the POLR2A gene. Analysis using qRT-PCR confirmed reduced POLR2A mRNA in KICRi002A-5 vs. the isogenic WT iPSC line. The edited iPSC line expressed pluripotency markers and exhibited differentiation capacity into the three germ layers. Assessment of genomic integrity revealed a normal karyotype and OFF-target editing was excluded. The iPSC line KICRi002A-5 provides a useful resource to study mechanisms underlying developmental defects caused by RBP1 insufficiency.

PubMed 34688129

DOI 10.1016/j.scr.2021.102577

Crossref 10.1016/j.scr.2021.102577

pii: S1873-5061(21)00424-4