Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [bulk RNA-seq]

ABSTRACT: HIV-Associated Neurocognitive Disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a proper model. We developed a human-induced pluripotent stem cell (HiPSC) based model, independently differentiating HiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV-infection and ART. Single cell RNAseq analysis on tri-cultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Treatment with the antiretroviral compound EFZ mostly resolved these signatures. However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in TNFa production by microglia. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of infection, its treatment, and other co-morbid conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE143685 | GEO | 2020/04/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [scRNA-seq]

Project description:HIV-Associated Neurocognitive Disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a proper model. We developed a human-induced pluripotent stem cell (HiPSC) based model, independently differentiating HiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV-infection and ART. Single cell RNAseq analysis on tri-cultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Treatment with the antiretroviral compound EFZ mostly resolved these signatures. However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in TNFa production by microglia. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of infection, its treatment, and other co-morbid conditions.

2020-04-27 | GSE143686 | GEO

Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1 [iPSCMG_TFS]

Project description:HIV-associated neurocognitive disorders (HAND) persist as a notable cause of illness among individuals with HIV. Despite significant progress in antiretroviral therapy (ART), HAND continues to be a major concern, impacting approximately one-third of those infected with HIV. Recent research underscores the pivotal role of microglia, the primary immune cells in the central nervous system (CNS), in the development and progression of HAND. The infection and activation of microglia by HIV leads to the release of pro-inflammatory markers, cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS). These factors collectively initiate signalling pathways that contribute to neuroinflammation, a central process in the development of HAND. In order to validate stem cell-derived microglia (iMGL) as a viable model system for HAND investigation, we infected iMGLs and human monocyte-derived macrophages (MDMs) with the primary HIV-1 isolate Ba-L at an MOI of 0.25. Total RNA was extracted from cell populations on days 1, 2, 4, 6, and 8 following infection. Subsequently, we conducted bulk RNA sequencing to examine the longitudinal transcriptomic alterations induced by the virus over this time frame

2024-05-01 | GSE248998 | GEO

Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1 [iPSCMG]

2024-05-01 | GSE248997 | GEO

Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1 [MDM]

2024-05-01 | GSE248996 | GEO

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

Project description:Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed microarray analysis using Affymetrix Arrays in portmortem brain tissues from seven treated and eight untreated HAND patients and six uninfected controls.

2011-09-24 | E-GEOD-28160 | biostudies-arrayexpress

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

2011-09-25 | GSE28160 | GEO

Differential Gene Expression in HIV-Infected Individuals Following ART.

Project description:A paired analysis of peripheral blood mononuclear cells (PBMCs) isolated before and after antiretroviral therapy (ART) from a robust number of HIV-infected patients (N=36). Results identify a total of 4,157 DEGs following ART in HIV-infected participants and the transition from a period of active virus replication before ART to one of viral suppression This study evaluated PBMC gene expression in cells from 36 (4 dropped from analysis) recently HIV-infected individuals to identify differentially expressed genes following 48 weeks of ART

2013-09-10 | E-GEOD-44228 | biostudies-arrayexpress

Differential Gene Expression in HIV-Infected Individuals Following ART.

2013-09-10 | GSE44228 | GEO

HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

Project description:Exploratory microarray analysis identified significant changes in gene expression in adipose tissue. These included changes in genes regulating lipid and steroid metabolic processes and electron carrier activity in HIV-infected patients receiving antiretroviral therapy (ART). Additional genes involved in metabolic processes and mitochondrial function were found to be up-regulated in the adipose tissue of HIV-positive patients compared with HIV-negative controls. To identify differential gene expression in different tissues (PBMC, muscle, adipose tissue) between HIV patient groups (HIV negative, HIV positive with ART, HIV positive without ART).

2011-07-07 | E-GEOD-30310 | biostudies-arrayexpress

Profound phenotypic and epigenetic heterogeneity of the HIV-1 infected CD4+ T cell reservoir

Project description:Understanding the complexity of the long-lived HIV reservoir during antiretroviral therapy (ART) remains a major impediment for HIV cure research. To address this, we developed single-cell viral ASAPseq to precisely define the unperturbed peripheral blood HIV-infected memory CD4+ T cell reservoir from antiretroviral treated people living with HIV (ART-PLWH) via the presence of integrated accessible proviral DNA in concert with epigenetic and cell surface protein profiling. We identified profound reservoir heterogeneity within and between ART-PLWH, characterized by novel and known surface markers within total and individual memory CD4+ T cell subsets. We further uncovered novel epigenetic profiles and transcription factor motifs enriched in HIV-infected cells that suggest infected cells with accessible provirus, irrespective of reservoir distribution, are poised for reactivation during ART treatment. Together, our findings reveal the extensive inter- and intrapersonal cellular heterogeneity of the HIV reservoir, and establish an initial multiomic atlas to develop targeted reservoir elimination strategies.

2022-10-21 | GSE199727 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data