Prdm16os is a brain and astrocyte-specific lncRNA implicated with Alzheimer’s disease
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1130444 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29665072.fastq.gz | Fastqsanger.gz | |||
| SRR29665073.fastq.gz | Fastqsanger.gz | |||
| SRR29665074.fastq.gz | Fastqsanger.gz | |||
| SRR29665075.fastq.gz | Fastqsanger.gz | |||
| SRR29665076.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Astrocytes provide crucial support for neurons, contributing to synaptogenesis, synaptic maintenance, and neurotransmitter recycling. Under pathological conditions, deregulation of astrocytes contributes to neurodegenerative diseases such as Alzheimer’s disease (AD), highlighting the growing interest in targeting astrocyte function to address early phases of AD pathogenesis. While most research in this field has focused on protein-coding genes, non-coding RNAs, particularly long non-coding RNAs (lncRNAs), have emerged as significant regulatory molecules. In this study, we identified the lncRNA PRDM16-DT as highly enriched in the human brain, where it is almost exclusively expressed in astrocytes. PRDM16-DT and its murine homolog, Prdm16os, are downregulated in the brains of AD patients and in AD models. In line with this, knockdown of PRDM16-DT and Prdm16os revealed its critical role in maintaining astrocyte homeostasis and supporting neuronal function by regulating genes essential for glutamate uptake, lactate release, and neuronal spine density through interactions with the RE1-Silencing Transcription factor (Rest) and Polycomb Repressive Complex 2 (PRC2). Notably, CRISPR-mediated overexpression of Prdm16os mitigated functional deficits in astrocytes induced by stimuli linked to AD pathogenesis. These findings underscore the importance of PRDM16-DT in astrocyte function and its potential as a novel therapeutic target for neurodegenerative disorders characterized by astrocyte dysfunction.
2025-01-03 | GSE271196 | GEO
Project description:Proteome analysis of isolated mouse brain blood vessels and perivascular astrocyte endfeet (PV-AEF) using DIA.
2023-11-04 | PXD037949 | JPOST Repository
Project description:Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer’s disease (AD) neuropathology remain largely unexplored. Here, we performed single- nucleus RNA-sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology, across 32 donors spanning the entire normal aging-to-severe AD continuum. We discovered astrocyte gene expression trajectories that are differentially activated or suppressed at various regions and disease stages. We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across the AD-vulnerable neural network (spatial axis) or AD pathology stage (temporal axis). The proportion of homeostatic, intermediate, and reactive astrocytes changed solely along the spatial axis, whereas two other unique subclusters changed along the temporal axis. One of these, a trophic factor-rich subcluster, declined along pathology stage, whereas the other, defined by proteostasis and metabolic genes, increased in late-stage but unexpectedly returned to baseline levels in end-stage, suggesting exhaustion of response with chronic exposure to neuropathology. Our study underscores the complex and dynamic nature of astrocytic responses in AD and our findings are available at https://ad-progression-atlas.partners.org
2024-07-22 | GSE268599 | GEO
Project description:Astrocytes provide crucial support for neurons, contributing to synaptogenesis, synaptic maintenance, and neurotransmitter recycling. Under pathological conditions, deregulation of astrocytes contributes to neurodegenerative diseases such as Alzheimer's disease (AD), highlighting the growing interest in targeting astrocyte function to address early phases of AD pathogenesis. While most research in this field has focused on protein-coding genes, non-coding RNAs, particularly long non-coding RNAs (lncRNAs), have emerged as significant regulatory molecules. In this study, we identified the lncRNA PRDM16-DT as highly enriched in the human brain, where it is almost exclusively expressed in astrocytes. PRDM16-DT and its murine homolog, Prdm16os, are downregulated in the brains of AD patients and in AD models. In line with this, knockdown of PRDM16-DT and Prdm16os revealed its critical role in maintaining astrocyte homeostasis and supporting neuronal function by regulating genes essential for glutamate uptake, lactate release, and neuronal spine density through interactions with the RE1-Silencing Transcription factor (Rest) and Polycomb Repressive Complex 2 (PRC2). Notably, CRISPR-mediated overexpression of Prdm16os mitigated functional deficits in astrocytes induced by stimuli linked to AD pathogenesis. These findings underscore the importance of PRDM16-DT in astrocyte function and its potential as a novel therapeutic target for neurodegenerative disorders characterized by astrocyte dysfunction.
| S-EPMC11244882 | biostudies-literature
Project description:By analyzing 250 astrocyte single cell transcriptomes from adult brain, we provide gene expresssion profile of brain astrocyte
2017-12-06 | GSE99058 | GEO
Project description:Genetic studies implicate Clusterin (CLU) in the pathogenesis of Alzheimer’s disease (AD), yet its precise molecular impact remains unclear. Through unbiased proteomic profiling and functional validation in CLU-deficient astrocytes, we identify increased NfkB-dependent signaling and complement C3 secretion. Reduction of astrocyte CLU induced microglia dependent modulation of extracellular APOE and phosphorylated tau, as well as increased microglial phagocytosis and reduced synapse numbers. By integrating mouse and human cellular models with comprehensive analyses of human plasma and brain tissue, we demonstrate that CLU AD risk alleles are associated with reduced CLU protein and heightened inflammatory profiles. These findings establish a mechanistic link between AD genetic risk factors, astrocyte reactivity, and microglia-mediated effects on synaptic integrity. Collectively, these results support a model in which CLU upregulation in response to neuropathology is associated with maintenance of cognitive function, while diminished astrocyte CLU levels heighten disease susceptibility.
2025-04-28 | GSE294133 | GEO
Project description:Genetic studies implicate Clusterin (CLU) in the pathogenesis of Alzheimer’s disease (AD), yet its precise molecular impact remains unclear. Through unbiased proteomic profiling and functional validation in CLU-deficient astrocytes, we identify increased NfkB-dependent signaling and complement C3 secretion. Reduction of astrocyte CLU induced microglia dependent modulation of extracellular APOE and phosphorylated tau, as well as increased microglial phagocytosis and reduced synapse numbers. By integrating mouse and human cellular models with comprehensive analyses of human plasma and brain tissue, we demonstrate that CLU AD risk alleles are associated with reduced CLU protein and heightened inflammatory profiles. These findings establish a mechanistic link between AD genetic risk factors, astrocyte reactivity, and microglia-mediated effects on synaptic integrity. Collectively, these results support a model in which CLU upregulation in response to neuropathology is associated with maintenance of cognitive function, while diminished astrocyte CLU levels heighten disease susceptibility.
2025-04-28 | GSE289565 | GEO
Project description:Normal brain aging is marked by a cognitive decline, spurred by changes in cellular metabolism and homeostatic dysregulation, as well as modifications in synapses and neuronal connectivity. Astrocytes are well positioned as an effector of these changes, although how properties of astrocytes change with age remains unclear. Here, we address this question by profiling astrocytic gene expression from multiple brain regions of adult (4 month-old) and aged (2 years-old) mice. We isolated mRNA from transgenic mice where ribosomes within astrocytes were genetically tagged (GFAP-cre x RPL22-HA, astrocyte ribotag). We then used RNA sequencing to identify and quantify the astrocyte-enriched mRNA, analyzing 4 different brain regions: visual cortex, somatomotor cortex, hypothalamus, and cerebellum. Overall, we find that astrocyte expression of inflammatory and immune response factors increase with age, as well as changes in genes associated with metabolism, cholesterol synthesis, and synaptogenesis. Going forward, these data contribute to an understanding of astrocyte diversity and provide insight into the role of astrocytes in normal aging.
2017-12-11 | GSE99791 | GEO
Project description:Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer’s disease (AD) risk, but its functions are not fully understood. Here, we found that medial prefrontal cortex (mPFC) injection with chondroitinase ABC (ChABC) to remodel ECM reverses short-term memory loss and reduces Aβ deposition in 5xFAD mice. ECM remodeling also reactivates astrocytes, untangles aggrecan’s entanglement with amyloid-beta (Aβ) plaques, and encourages astrocyte recruitment to the surrounding plaques. ECM remodeling promotes astrocyte phagocytosis of Aβ plaque by activating the astrocyte phagocytosis receptor mertk and astrocytic vesicle circulation. Importantly, ECM remodeling enhances the autophagy-lysosome pathway in astrocytes to mediate Aβ clearance and alleviate AD pathology. Our work thus discovers a cellular mechanism to remodel the ECM to active astrocyte autophagic lysosomal pathway alleviation AD pathology. It may represent a potential therapeutic strategy and serve as a hallmark for treating AD.
2024-10-17 | PXD046784 | Pride
Project description:The templated misfolding of tau proteins accounts for tau pathology spread in Alzheimer’s disease (AD). Post-translational modifications, including phosphorylation at specific residues, are closely linked with tau seeding ability and clinical disease progression. This study investigates the role of astrocytes in tau spread, demonstrating that tau aggregates from post-mortem AD brain are internalized and processed by human astrocytes. Differences in tau internalization, clearance, and seeding were observed, potentially reflecting the molecular properties of tau. A direct relationship between tau handling by astrocytes and astrocyte responses was noted in transcriptomic data, highlighting dysregulated genes linked to pathological tau clearance pathways. To explore these differences, mass spectrometry was performed on both control and AD brain extracts, providing insights into the complex interplay between tau diversity and astrocyte responses in AD.
2025-05-07 | PXD056614 | Pride