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Series GSE135707 Query DataSets for GSE135707
Status Public on Oct 08, 2019
Title PSEN1ΔE9, APPswe and APOE4 confer disparate phenotypes in human iPSC-derived microglia
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Here we elucidate the effect of Alzheimer’s disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9 and APPswe, on functionality of human microglia. We present a physiologically relevant high-yield protocol for producing human microglia-like cells (iMGLs) from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to recreate microglial ontogeny from yolk sac. The iMGLs express microglial signature genes and respond to ADP with intracellular Ca2+ release distinguishing them from macrophages. Using 16 iPSC lines from healthy donors, AD patients and isogenic controls, we reveal that the APOE4 genotype has a profound impact on several aspects of microglial functionality whereas PSEN1ΔE9 and APPswe mutations trigger minor alterations. The APOE4 genotype impairs phagocytosis, migration and metabolic activity of iMGLs but exacerbates their cytokine secretion. This indicates that APOE4 iMGLs are fundamentally unable to mount normal microglial functionality in AD.
Overall design Human iPSC-derived microglia-like cells were collected and analyzed for gene expression using RNA-seq.
Contributor(s) Konttinen H, Malm T
Citation(s) 31522977
Submission date Aug 12, 2019
Last update date Nov 12, 2019
Contact name Tarja Malm
Organization name University of Eastern Finland
Department A.I. Virtanen Institute for Molecular Sciences
Lab Tarja Malm Lab
Street address Neulaniementie 2
City Kuopio
ZIP/Postal code 70211
Country Finland
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (12)
GSM4026496 iPSC-microglia 1 rep 1
GSM4026497 iPSC-microglia 2 rep 1
GSM4026498 iPSC-microglia 3 rep 1
BioProject PRJNA559812
SRA SRP218087

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Supplementary file Size Download File type/resource
GSE135707_RAW.tar 26.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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