PXD020240

PXD020240 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Multi-omic comparison of Alzheimers variants in human ESC-derived microglia reveals convergence at APOE
Description	Variations in many genes linked to sporadic Alzheimers disease (AD), show abundant expression in microglia, however, relationships between these genes remain largely elusive. Here, we establish isogenic human ES-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1 and TREM2 loci, and curate a comprehensive atlas comprising ATACseq, ChIPseq, RNAseq and proteomics datasets. AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates upregulation of APOE as a convergent pathogenic node. We also observe cross-regulatory relationships between SORL1 and TREM2, where SORL1R744X hMGLs induce TREM2 expression to enhance APOE expression. AD-associated SORL1 and TREM2 mutations also impaired hMGL A-beta uptake in an APOE-dependent manner in vitro, and attenuated A-beta uptake/clearance in mouse AD brain xenotransplants. Utilizing this modeling and analysis platform for human microglia, we provide new insight into epistatic interactions in AD genes and demonstrate convergence of microglial AD genes at the APOE locus
HostingRepository	MassIVE
AnnounceDate	2020-09-14
AnnouncementXML	Submission_2020-09-14_16:34:50.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexandre Rosa Campos
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-07 16:00:24	ID requested
⏵ 1	2020-09-14 16:34:51	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: human microglia, APOE, SORL1, TREM2, Alzheimers disease

submitter keyword: human microglia, APOE, SORL1, TREM2, Alzheimers disease

Contact List

Timothy Y. Huang
contact affiliation	Sanford Burnham Prebys Medical Discovery Institute
contact email	thuang@sbpdiscovery.org
lab head
Alexandre Rosa Campos
contact affiliation	SBP Medical Discovery Institute
contact email	arosacampos@sbpdiscovery.org
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000085698/