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RNA Sequencing Facilitates Quantitative Analysis of Lupus (MRL/lpr) and Control（MRL/mpj）Mouse Microglia Tanscriptomes

ABSTRACT: RNA Sequencing Facilitates Quantitative Analysis of Lupus (MRL/lpr) and Control（MRL/mpj）Mouse Microglia Tanscriptomes

PROVIDER: PRJNA830717 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18885515_1.fastq.gz	Fastqsanger.gz
	SRR18885515_2.fastq.gz	Fastqsanger.gz
	SRR18885516_1.fastq.gz	Fastqsanger.gz
	SRR18885516_2.fastq.gz	Fastqsanger.gz
	SRR18885517_1.fastq.gz	Fastqsanger.gz

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RNA Sequencing Facilitates Quantitative Analysis of Lupus (MRL/lpr) and Control（MRL/mpj）Mouse Microglia Tanscriptomes

Project description:Up to 75% of systematic lupus erythematosus (SLE) patients experience neuropsychiatric (NP) symptoms, called neuropsychiatric SLE (NPSLE), yet the underlying mechanisms remain elusive. Microglia control synaptic pruning during early postnatal brain development. The process in NPSLE remains unclear. Here, we show that microglia-coordinated elimination of synaptic terminals participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We elucidated that lupus mice developed increased depression- and anxiety-like behaviors and persistent phagocytic microglia reactivation before overt peripheral lupus pathology. Microglial engulfment of synapses explained behavioral disorders. To elucidate the mechanism of synaptic pruning by microglia, we sequenced the gene expression in sorted microglia from both lupus (MRL/lpr) mice and the wild-type (MRL/mpj) controls.

2024-03-27 | GSE201282 | GEO

RNA Sequencing Facilitates Quantitative Analysis of Wild Type(MRL-mpj) and MRL-lpr (PBS or MSC treated) Hippocampoal Transcriptomes

Project description:Up to 75% of systematic lupus erythematosus (SLE) patients experience neuropsychiatric (NP) symptoms, called neuropsychiatric SLE (NPSLE), yet the underlying mechanisms remain elusive. Complement cascades mediate synaptic pruning by microglia during early postnatal brain development. The process in NPSLE remains unclear. Here, we show that complement-coordinated elimination of synaptic terminals participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We elucidated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglia reactivation before overt peripheral lupus pathology. Microglial engulfment of synapses explained behavioral disorders. We further determined that neuronal Nr4a1 signaling was essential for attracting C1q synaptic deposition then apposition of phagocytic microglia, ensuing synaptic loss and neurological disease. Minocycline-deactivated microglia, antibody-blocked C1q, or neuronal Nr4a1 restore protected lupus mice from synapse loss and NP manifestations. Our findings revealed an active role of neurons in coordinating microglia-mediated synaptic loss and highlight neuronal Nr4a1 and C1q as critical components amenable to pharmacological intervention.

2022-02-23 | GSE154288 | GEO

Identification of common lupus-disease related microRNA expression pattern in three different murine models of lupus

Project description:In this study, miRNA expression in splenic lymphocytes from three genetically disparate lupus-prone mouse models (MRL-lpr, B6-lpr and NZB/WF1) were profiled. 49 miRNAs were found to be differentially expressed in MRL-lpr mice compared to MRL mice; and 24 miRNAs were differentially expressed in B6-lpr mice compared to B6 mice. Among these dysregulated miRNAs, we noted that 15 miRNAs were common to both lpr strains. Interestingly, microarray analysis of NZB/W and NZW at 3 months of age, an age when overt lupus disease is not evident in NZB/W mice, revealed that only one miRNA, miR-148a was significantly upregulated in NZB/W mice. The aim of this porject is to determine the common miRNA expression changes in splenocytes from different strains of murine lupus models. The splenocytes were prepared from genetically lupus-prone female mice including MRL/MpJ-Faslpr/J (MRL-lpr), NZBWF1/J (NZB/W), B6.MRL-Faslpr/J (B6-lpr) and their control mice MRL/MpJ (MRL), NZW/LacJ (NZW) and C57BL/6J (B6) mice (The Jackson laboratory, ME). Total RNAs, containing miRNAs were isolated from whole splenocytes using mirVana miRNA isolation kits (Ambion) following manufactory’s instructions and sent to LC Sciences (http://www.lcsciences.com/) for the microarray assay. The mouse miRNA array chips (Chip ID miRMouse 12.0 version), which included 617 unique, mature, mouse miRNA, based on the Sanger miRBase Release 12.0, were used in the assay.

2011-12-17 | E-GEOD-22359 | biostudies-arrayexpress

MicroRNA profiling by PCR array of mouse Treg cells from non-autoimmune C3H/HeOuj and lupus prone MRL/lpr strains

Project description:Comparison of Treg miRNA expression between non-autoimmune C3H/HeOuj and lupus prone MRL/lpr mice

2011-11-30 | E-MEXP-2954 | biostudies-arrayexpress

Diagnosis and early detection of CNS-SLE in MRL/lpr mice using peptide microarrays (GPL14921)

Project description:We investigated whether mouse serum autoantibody binding patterns on random-sequence peptide microarrays (immunosignaturing) can be used for diagnosing and predicting the onset of lupus and its central nervous system (CNS) manifestations. Submitter states "We have no processed data to submit. We have no gpr files to submit." To identify possible predictive and diagnostic peptides of lupus and CNS-lupus, we carried out two studies and selected peptides in common across both studies. In the first study we tested 3-6 MRL/lpr, MRL/mp and C3H/HeJ mice at four months of age. For study two we tested 9-10 MRL/lpr and MRL/mp at 1.5 and 4 months of age. In both studies the mice sera were diluted 1/500 and analyzed using microarray peptides from platform GPL14921. We ran each sample in triplicate. The MRL/lpr and MRL/mp are the autoimmune strains and the C3H/HeJ is the control strain.

2014-05-08 | E-GEOD-57388 | biostudies-arrayexpress

Evaluation of microRNA levels in recipient BMMSCs of MRL/lpr mice after cell therapy (miRNA)

Project description:Mesenchymal stem cell transplantation (MSCT) has been widely used to treat a variety of human diseases. However, the detailed mechanisms underlying its success are not fully understood. Here we show that MSCT rescues recipient bone marrow mesenchymal stem cell (BMMSC) function in Fas-deficient-MRL/lpr systemic lupus erythematosus (SLE) mice via a miR-29b/Dnmt1/Notch epigenetic cascade. Using the microRNA microarray, we found that MSCT could rescue the high level of miR-29b in the recipient BMMSCs of MRL/lpr mice. In the present study, mesenchymal stem cell transplantation (MSCT) was used to treat MRL/lpr mice. One week after the treatment, normal control MSCs from C3H/HeJ mice (C3H), recipient MSCs from untreated MRL/lpr mice (LPR) and recipient MSCs from MSCT-treated MRL/lpr mice (MSC) were used for total RNA extraction and microRNA microarray for analysis of microRNA expressions.

2014-03-20 | E-GEOD-55971 | biostudies-arrayexpress

Evaluation of global methylation profile in recipient BMMSCs of MRL/lpr mice after cell therapy (MeDip)

Project description:Mesenchymal stem cell transplantation (MSCT) has been widely used to treat a variety of human diseases. However, the detailed mechanisms underlying its success are not fully understood. Here we show that MSCT rescues recipient bone marrow mesenchymal stem cell (BMMSC) function in Fas-deficient-MRL/lpr systemic lupus erythematosus (SLE) mice via rescuing their hypomethylated DNA profile. Using the methylation microarray, we found the global hypomethylation pattern in the recipient BMMSCs of MRL/lpr mice could be rescued by MSCT. In the present study, mesenchymal stem cell transplantation (MSCT) was used to treat MRL/lpr mice. One week after the treatment, normal control MSCs from C3H/HeJ mice (C3H), recipient MSCs from untreated MRL/lpr mice (LPR) and recipient MSCs from MSCT-treated MRL/lpr mice (MSC) were used for total DNA extraction and DNA methylation microarray for analysis of global genome methylation patterns.

2014-03-20 | E-GEOD-55970 | biostudies-arrayexpress

Evaluation of microRNA levels in recipient BMMSCs of MRL/lpr mice after cell therapy (miRNA)

2014-03-20 | GSE55971 | GEO

Evaluation of global methylation profile in recipient BMMSCs of MRL/lpr mice after cell therapy (MeDip)

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The Aggregates of Mesenchymal stem cell with Cadherin/IGF1 Functionalized PLGA composite Microparticles Improve Systemic Lupus Erythematosus Treatment in MRL/lpr mice

Project description:Mesenchymal stem cell (MSC) therapy is a promising candidate for systemic lupus erythematosus (SLE), while more researches are needed to further improve therapeutic efficacy. In this study, engineered MSC aggregates are composited with MSC and cadherin/IGF1 functionalized PLGA composite microparticles, and are able to stimulate the microenvironment in vivo and enhance MSC functions of immunoregulation and cytokine secretion. Comprehensive characterization of these PLGA composite microparticles coated with E-cadherin/N-cadherin, enhancing MSC viability and cytokine secretion, followed by transcriptomic analysis to evaluate their potential advantages. We detected engineered MSC aggregates further ameliorated skin and lupus nephritis, compared with MSCs in MRL/lpr mice. In addition, engineered MSC aggregates enhanced Treg differentiation in vitro and in the spleen and lumph node of MRL/lpr mice. These findings suggested that engineered MSC aggregates represented a promising bioengineered approach for treating SLE, broadening the clinical applications of MSC-based therapies.

2024-10-01 | GSE276961 | GEO

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