Generation and characterization of human induced pluripotent stem cell (hiPSC) lines from an Alzheimer's disease (ASUi003-A) and non-demented control (ASUi004-A) patient homozygous for the Apolipoprotein e4 (APOE4) risk variant

Nicholas Brookhouser,Ping Zhang,Richard Caselli,Jean J Kim,David A Brafman

doi:10.1016/j.scr.2017.07.003

Nicholas Brookhouser, Ping Zhang + Show 3 more

Open Access

https://doi.org/10.1016/j.scr.2017.07.003

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Abstract

Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers.

Highlights

The majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene
HiPSCs with various APOE genotypes will provide a valuable resource to study the mechanisms by which this risk factor contributes to AD onset and progression
Sequencing analysis of the human induced pluripotent stem cell (hiPSC) at the APOE gene in exon 4 confirm homozygosity at the e4 allele, identical to the parental peripheral blood mononuclear cells (PBMCs) [Fig. 1B; Note: Human APOE has three major isoforms, ApoE2, ApoE3, and ApoE4, which differ by two amino acid substitutions at residues 112 and 158 in exon 4—ApoE2 (Cys112, Cys158), ApoE3 (Cys112, Arg158), ApoE4 (Arg112, Arg158)]

Summary

Contents lists available at ScienceDirect

Generation and characterization of human induced pluripotent stem cell (hiPSC) lines from an Alzheimer's disease (ASUi003-A) and non-demented control (ASUi004-A) patient homozygous for the Apolipoprotein e4 (APOE4) risk variant. We generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers

Alternative names of stem cell lines

Resource utility

Genotype of locus

Embryoid body

Target SeV

Flow cytometry