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Series GSE129630 Query DataSets for GSE129630
Status Public on May 14, 2020
Title Human iPSC-derived microglia are genetically relevant to Alzheimer’s disease
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Microglia is a primary brain immune cell type that has been implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD) and neurodevelopmental disorders such as schizophrenia. Generating microglia from human induced pluripotent stem cells (hiPSC) has become an attractive approach to study the microglia-mediated causal mechanism of AD. Among other methods, Brownjohn et al. recently developed a particularly efficient and simple hiPSC-derived microglia (iMG) protocol. However, the transferability of this method to other labs, the transcriptomic similarity of these iMG to primary adult microglia, and their genetic relevance to AD remain unclear. With two hiPSC lines, we demonstrated that the Brownjohn method can efficiently give rise to iMG that were morphologically and functionally like microglia. Our pure iMG were also transcriptionally similar to previously reported iMG lines, as well as fetal and adult microglia. More importantly, we further showed the genetic relevance of iMG to AD using cell type-specific gene expression to partition disease heritability. Contrasting with neuronal and immune cell types, our iMG and several primary microglia and microglia-like cell types were all significantly enriched for AD relevant GWAS loci. These results supported the use of iMG as a valid human cellular model for understanding AD disease progression and a feasible mechanism for generation of AD patient-specific cell types for more precise in vitro analyses, and potentially more effective clinical care.
Overall design Two hiPSC cell lines were used for generation of samples, with collections of induced microglia and PMPs at various timepoints after plating cells. Three replicates that featured contamination of a fibroblast-like cell type are also included.
Contributor(s) Butler III RR, Kozlova A, Zhang H, Zhang S, Streit M, Sanders AR, Pang Z, Gejman PV, Duan J
Citation(s) 32399472
Submission date Apr 11, 2019
Last update date May 14, 2020
Contact name Robert Raymond Butler
Organization name Stanford University School of Medicine
Department Neurology & Neurological Sciences
Lab Longo
Street address 3172 Porter Dr., MC 5475
City Stanford
State/province CA
ZIP/Postal code 94304
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM3717626 CD11_1 iMG
GSM3717627 CD11_2 iMG
GSM3717628 CD11_3 iMG
BioProject PRJNA532337
SRA SRP191977

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Supplementary file Size Download File type/resource
GSE129630_raw_CD11-CD21_counts.txt.gz 565.9 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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