Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-Cell Transcriptome Profiling Reveals the Suppressive Role of Retinal Neurons in Microglia Activation Under Diabetes Mellitus.

ABSTRACT: Diabetic retinopathy, as one of the common complications of diabetes mellitus, is the leading cause of blindness in the working-age population worldwide. The disease is characterized by damage to retinal vasculature, which is associated with the activation of retina microglial and induces chronic neurodegeneration. Previous studies have identified the effects of activated microglial on the retinal neurons, but the cellular and molecular mechanisms underlying microglial activation is largely unknown. Here, we performed scRNA-seq on the retina of non-human primates with diabetes mellitus, and identified cell-type-specific molecular changes of the six major cell types. By identifying the ligand-receptor expression patterns among different cells, we established the interactome of the whole retina. The data showed that TNF-α signal mediated the activation of microglia through an autocrine manner. And we found TGFβ2, which was upregulated in cone dramatically by hyperglycemia, inhibited microglia activation at the early stage of diabetic retinopathy. In summary, our study is the first to profile cell-specific molecular changes and the cell-cell interactome of retina under diabetes mellitus, paving a way to dissect the cellular and molecular mechanisms underlying early-stage diabetic retinopathy.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC8381733 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Single-cell transcriptome profiling reveals the suppressive role of retinal neurons in microglia activation under diabetes mellitus

Project description:Diabetic retinopathy, as one of the common complications of diabetes mellitus, is the leading cause of blindness in working-age population. The disease is characterized by damage to retinal vasculature, which is associated with the activation of retina microglial and chronic neurodegeneration. Previous studies have identified the effects of activated microglial on the retinal neurons, but how the microglial activation is regulated by the others is largely unknown. Here, we performed scRNA-seq on the retina of non-human primates with diabetes mellitus, and identified cell-type-specific molecular changes of the six major cell types. By identifying the ligand-receptor expression patterns among different cells, we established the interactome of the whole retina. The data showed that TNF-α signal mediated the activation of microglial through an autocrine manner. We found Muller and amacrine acted through SPP1 signaling and cone acted through TGFβ signaling, to inhibit the genes related to microglial activation. Our study is the first to profile cell-specific molecular changes and the cell-cell interactome of retina under diabetes mellitus, paving a way to dissect the cellular and molecular mechanisms underlying early-stage diabetic retinopathy.

2021-08-05 | GSE168908 | GEO

Single-cell transcriptome profiling reveals the suppressive role of retinal neurons in microglia activation under diabetes mellitus

Project description:Single-cell transcriptome profiling reveals the suppressive role of retinal neurons in microglia activation under diabetes mellitus

| PRJNA714553 | ENA

Role of aldose reductase in diabetes-induced retinal microglia activation.

Project description:Diabetes-induced hyperglycemia plays a key pathogenic role in degenerative retinal diseases. In diabetic hyperglycemia, aldose reductase (AR) is elevated and linked to the pathogenesis of diabetic retinopathy (DR) and cataract. Retinal microglia (RMG), the resident immune cells in the retina, are thought to contribute to the proinflammatory phenotype in the diabetic eye. However, we have a limited understanding of the potential role of AR expressed in RMG as a mediator of inflammation in the diabetic retina. Glycated proteins accumulate in diabetes, including Amadori-glycated albumin (AGA) which has been shown to induce a proinflammatory phenotype in various tissues. In this study, we investigated the ability of AGA to stimulate inflammatory changes to RMG and macrophages, and whether AR plays a role in this process. In macrophages, treatment with an AR inhibitor (Sorbinil) or genetic knockdown of AR lowered AGA-induced TNF-α secretion (56% and 40%, respectively) as well as cell migration. In a mouse RMG model, AR inhibition attenuated AGA-induced TNF-α secretion and cell migration (67% and 40%, respectively). To further mimic the diabetic milieu in retina, we cultured RMG under conditions of hypoxia and observed the induction of TNF-α and VEGF protein expression. Downregulation of AR in either a pharmacological or genetic manner prevented hypoxia-induced TNF-α and VEGF expression. In our animal study, increased numbers of RMG observed in streptozotocin (STZ)-induced diabetic retina was substantially lower when diabetes was induced in AR knockout mice. Thus, in vitro and in vivo studies demonstrated that AR is involved in diabetes-induced RMG activation, providing a rationale for targeting AR as a therapeutic strategy for DR.

| S-EPMC6421082 | biostudies-literature

Single-cell transcriptome profiling of mouse cardio-pharyngeal development under maternal diabetes mellitus

Project description:We employed single cell RNA sequencing to interrogate the consequence of maternal diabetes in cardiac and craniopharyngeal development

2023-10-16 | GSE198901 | GEO

Aldose reductase mediates retinal microglia activation.

Project description:Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1(GFP) mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migration in vivo. When tested on an AR(WT) background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-? and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy.

| S-EPMC4836993 | biostudies-other

Single-cell profiling of mouse cardio-pharyngeal development under maternal diabetes mellitus

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-16 | GSE198905 | GEO

Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation.

Project description:Macular neovascularization type 3, formerly known as retinal angiomatous proliferation (RAP), is a hallmark of age-related macular degeneration and is associated with an accumulation of myeloid cells, such as microglia (MG) and infiltrating blood-derived macrophages (MAC). However, the contribution of MG and MAC to the myeloid cell pool at RAP sites and their exact functions remain unknown. In this study, we combined a microglia-specific reporter mouse line with a mouse model for RAP to identify the contribution of MG and MAC to myeloid cell accumulation at RAP and determined the transcriptional profile of MG using RNA sequencing. We found that MG are the most abundant myeloid cell population around RAP, whereas MAC are rarely, if ever, associated with late stages of RAP. RNA sequencing of RAP-associated MG showed that differentially expressed genes mainly contribute to immune-associated processes, including chemotaxis and migration in early RAP and proliferative capacity in late RAP, which was confirmed by immunohistochemistry. Interestingly, MG upregulated only a few angiomodulatory factors, suggesting a rather low angiogenic potential. In summary, we showed that MG are the dominant myeloid cell population at RAP sites. Moreover, MG significantly altered their transcriptional profile during RAP formation, activating immune-associated processes and exhibiting enhanced proliferation, however, without showing substantial upregulation of angiomodulatory factors.

| S-EPMC8998238 | biostudies-literature

Single-cell chromatin accessibility profiling of mouse cardio-pharyngeal development under maternal diabetes mellitus

Project description:We employed single cell ATAC sequencing to interrogate the consequence of maternal diabetes in cardiac and craniopharyngeal development

2023-10-16 | GSE198866 | GEO

Single-cell transcriptome profiling of mouse cardio-pharyngeal development under maternal diabetes mellitus

Project description:Single-cell transcriptome profiling of mouse cardio-pharyngeal development under maternal diabetes mellitus

| PRJNA817268 | ENA

RNAseq analysis of retinal microglia during early diabetes

Project description:We report the use of RNAseq to identify gene changes in isolated retinal microglia after 4 weeks of STZ-induced diabetes. At this early time point in diabetes induction, single retinal cell suspensions were sorted via FACS using a Cd11b-FITC conjugate. RNA was isolated and preamplified using the SMARTSeq v4 low RNA input kit. After library preparation a 50bp single end read was performed at a depth of 19-34 million reads per sample using the Illumina HiSeq. Constructs were mapped to the rat genome and differential expression calculated between the STZ-treated and control groups.

2021-12-16 | GSE139276 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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