Impact of c-JUN deficiency on thalamus development in mice and human neural models
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1019730 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26140800_1.fastq.gz | Fastqsanger.gz | |||
| SRR26140800_2.fastq.gz | Fastqsanger.gz | |||
| SRR26140801_1.fastq.gz | Fastqsanger.gz | |||
| SRR26140801_2.fastq.gz | Fastqsanger.gz | |||
| SRR26140802_1.fastq.gz | Fastqsanger.gz |
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Project description:c-Jun is a gene expression regulator. By forming homo- or heterodimer, c-Jun binds to DNA and regulates gene transcription. c-Jun is deeply involved in embryonic development but its effect on nervous system development especially in higher mammal is unclear. In this study, we combined H1ESC derived neural progenitor cells (NPCs), cerebral organoids (COs) and mouse model to study the role of c-Jun in early nervous system development. c-Jun KO promoted NPCs induction and differentiation while weakened NPCs’ adhesion ability. c-Jun KO COs got more robust neural ectoderm and expanded Pax6+/Nestin+ cortex-like layer while less tight junctional core. c-Jun KO mouse embryos on E14.5 showed malformation of thalamus in diencephalon with tight junction loose and cell lose. Taken together, the consistent trend in three models implied that c-Jun deletion promoted neural differentiation while weakened the tight junctions. The thalamus/diencephalon was vulnerable to dysplasia when lose c-Jun in early mouse embryonic development.
2024-12-20 | GSE243735 | GEO
Project description:c-Jun is a gene expression regulator. By forming homo- or heterodimer, c-Jun binds to DNA and regulates gene transcription. c-Jun is deeply involved in embryonic development but its effect on nervous system development especially in higher mammal is unclear. In this study, we combined H1ESC derived neural progenitor cells (NPCs), cerebral organoids (COs),Thalamus Organoids(ThOs) and mouse model to study the role of c-Jun in early nervous system development. c-Jun KO promoted NPCs induction and differentiation while weakened NPCs’ adhesion ability. c-Jun KO COs got more robust neural ectoderm and expanded Pax6+/Nestin+ cortex-like layer while less tight junctional core. c-Jun KO mouse embryos on E14.5 showed malformation of thalamus in diencephalon with tight junction loose and cell lose. Taken together, the consistent trend in three models implied that c-Jun deletion promoted neural differentiation while weakened the tight junctions. The thalamus/diencephalon was vulnerable to dysplasia when lose c-Jun in early mouse embryonic development.
2024-12-20 | GSE260732 | GEO
Project description:Impact of c-JUN deficiency on thalamus development in mice and human neural models [ATACseq, RNAseq, CUT&Tag]
| PRJNA1083042 | ENA
Project description:Backgroundc-Jun is a key regulator of gene expression. Through the formation of homo- or heterodimers, c-JUN binds to DNA and regulates gene transcription. While c-Jun plays a crucial role in embryonic development, its impact on nervous system development in higher mammals, especially for some deep structures, for example, thalamus in diencephalon, remains unclear.MethodsTo investigate the influence of c-JUN on early nervous system development, c-Jun knockout (KO) mice and c-JUN KO H1 embryonic stem cells (ESCs)-derived neural progenitor cells (NPCs), cerebral organoids (COs), and thalamus organoids (ThOs) models were used. We detected the dysplasia via histological examination and immunofluorescence staining, omics analysis, and loss/gain of function analysis.ResultsAt embryonic day 14.5, c-Jun knockout (KO) mice exhibited sparseness of fibers in the brain ventricular parenchyma and malformation of the thalamus in the diencephalon. The absence of c-JUN accelerated the induction of NPCs but impaired the extension of fibers in human neuronal cultures. COs lacking c-JUN displayed a robust PAX6+/NESTIN+ exterior layer but lacked a fibers-connected core. Moreover, the subcortex-like areas exhibited defective thalamus characteristics with transcription factor 7 like 2-positive cells. Notably, in guided ThOs, c-JUN KO led to inadequate thalamus patterning with sparse internal nerve fibers. Chromatin accessibility analysis confirmed a less accessible chromatin state in genes related to the thalamus. Overexpression of c-JUN rescued these defects. RNA-seq identified 18 significantly down-regulated genes including RSPO2, WNT8B, MXRA5, HSPG2 and PLAGL1 while 24 genes including MSX1, CYP1B1, LMX1B, NQO1 and COL2A1 were significantly up-regulated.ConclusionOur findings from in vivo and in vitro experiments indicate that c-JUN depletion impedes the extension of nerve fibers and renders the thalamus susceptible to dysplasia during early mouse embryonic development and human ThO patterning. Our work provides evidence for the first time that c-JUN is a key transcription regulator that play important roles in the thalamus/diencephalon development.
| S-EPMC11662577 | biostudies-literature
Project description:Nuclei of the mammalian thalamus are aggregations of neurons with unique architectures and input-output connections, yet the molecular determinants of their organizational specificity remain unknown. By comparing expression profiles of thalamus and cerebral cortex in adult rhesus monkeys we identified transcripts that are unique to dorsal thalamus or to individual nuclei within it. Real-time quantitative polymerase chain reaction and in situ hybridization analyses confirmed the findings. Expression profiling of individual nuclei microdissected from the dorsal thalamus revealed additional subsets of nucleus-specific genes. Functional annotation using Gene Ontology (GO) vocabulary and Ingenuity Pathway analysis revealed over-representation of GO categories related to development, morphogenesis, cell-cell interactions, and extracellular matrix within the thalamus- and nucleus-specific genes-many involved in the Wnt signaling pathway. Examples included the transcription factor TCF7L2, localized exclusively to excitatory neurons, a calmodulin-binding protein PCP4, the bone extracellular matrix molecules SPP1 and SPARC, and other genes involved in axon outgrowth and cell matrix interactions. Other nucleus-specific genes such as CBLN1 are involved in synaptogenesis. The genes identified likely underlie nuclear specification, cell phenotype and connectivity during development and their maintenance in the adult thalamus. Experiment Overall Design: To determine the molecular underpinnings of nuclear specificity in the dorsal thalamus we isolated micro-punches of tissue from nucleus-specific regions and processed them for microarray analysis. Replicate samples from 5 separate dorsal thalamic nuclei were processed and compared to identify genes unique to each region. Affymetrix U133A Gene Chips were used. All of the samples were isolated from untreated adult monkey brain.
2008-06-15 | E-GEOD-6708 | biostudies-arrayexpress
Project description:Analysis of thalamus and hypothalamus under conditions of visual deprivation by dark-rearing (DR). Animals subjected to DR from birth till postnatal day (P) 14. Results provide insight into the role of visual inputs in the regulation of gene expression in thalamus and hypothalamus during development. RNA sample was taken from thalamus and hypothalamus of 14-day-old mouse reared in standard or dark condition. Comparisons among groups were made by one-color method with normalized data from Cy3 channels for data analysis.
2014-01-26 | E-GEOD-53136 | biostudies-arrayexpress
Project description:To further dissect whether and how activated JUN reconfigures the chromatin landscape, we performed Chromatin Immunoprecipitation (ChIP)-seq analyses for H3K4me1 and H3K27ac. Based on the significant increase of H3K27ac levels at H3K4me1+ sites, we identified 3,017 JUN-activated enhancers in JUN WT cells. In contrast, JUN AA fails to significantly induce H3K27ac accumulation at these regions. Their enrichment levels at JUN-activated enhancers were significantly decreased after JNKi treatment. Besides, these enhancers are directly driven by JUN, especially phosphorylated JUN.
2022-12-09 | GSE196345 | GEO
Project description:Haploinsufficiency of the progranulin (PGRN) protein is a leading cause of frontotemporal lobar degeneration (FTLD). Mouse models have been developed to study PGRN functions. However, PGRN deficiency in the commonly used C56BL/6 mouse strain background leads to very mild phenotypes, and pathways regulating PGRN deficiency phenotypes remain to be elucidated. We generated PGRN-deficient mice in the FVB/N background and compared PGRN deficiency phenotypes between C56BL/6 and FVB/N background via immunostaining, western blot, RNA-seq, and proteomics approaches. We also identified sPLA2-IIA as a novel binding partner of PGRN and demonstrated the importance of sPLA2-IIA in modifying PGRN deficiency phenotypes using inhibitor treatment and AAV-mediated overexpression in mouse models. We report that PGRN loss in the FVB/N mouse strain results in earlier onset and stronger FTLD-related and lysosome-related phenotypes. We found that PGRN interacts with sPLA2-IIA, a member of the secreted phospholipase A2 (sPLA2) family member and a key regulator of inflammation that is expressed in FVB/N but not C56BL/6 background. sPLA2-IIA inhibition rescues PGRN deficiency phenotypes and sPLA2-IIA overexpression drives enhanced gliosis and lipofuscin accumulation in PGRN-deficient mice. Additionally, RNA-seq and proteomics analysis revealed that mitochondrial pathways are upregulated in the PGRN-deficient C57BL/6 mice but not in the FVB/N mice. Our studies establish a better mouse model for FTLD-GRN and uncover novel pathways modifying PGRN deficiency phenotypes.
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Project description:To examine the effects of phosphorylated JUN-mediated enhancers activation on gene expression, we conducted RNA-seq analysis in JUN wildtype (WT) or JUN inactive mutant (JUN AA) overexpressed MRC5 cells. The expression levels of genes associated with JUN-activated enhancers are significantly upregulated in JUN WT cells rather than in JUN AA cells. To quantify the effects of JUN inactivation on gene expression, we also performed RNA-seq analysis in JNKi-treated induced CAFs (iCAFs). We observed that JNKi significantly reduced expression levels of JUN-activated enhancers-associated genes.
2022-12-09 | GSE196351 | GEO
Project description:Genome-wide maps of H3K27ac, H3K4me1, JUN and p-JUN in JUN overexpressed or JUN inactivated fibroblasts
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