Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cortical astrocytic neogenin, a key protein switching HIF1/2ɑ-VEGFa-induced angiogenesis to MEGF10-driven phagocytosis

ABSTRACT: Astrocytes play key roles in multi-cellular processes in the brain, including maintaining homeostasis of blood vessels (BVs) and clearance of damaged cell debris. The detailed underlying mechanisms remain elusive. Here, we provide evidence that cortical astrocytic neogenin (NEO1) coordinates MEGF10-mediated phagocytosis with HIF1/2ɑ driven VEGFa-induced angiogenesis. Knocking-out (KO) NEO1 in astrocytes increases in HIF1/2ɑ, VEGFa, and immature BVs, but decreases in MEGF10 and MEGF10-regulated phagocytosis, in mouse cortex, but not hippocampus. Further studies suggest that the NEO1-KO impairs prolyl hydroxylase domain protein (PHD) mediated HIF1/2ɑ hydroxylation by inducing iron deficiency, thus increasing HIF1/2ɑ-HIF1b-P300 protein complex driven VEGFa expression at the expense of HIF1β-P300 binding to the MEGF10 promoter; consequently, reducing MEGF10 expression. Thus, these results suggest that cortical astrocytic NEO1 promotes MEGF10 mediated phagocytosis, likely by suppressing HIF1/2ɑ-HIF1β-P300 induced VEGFa.

ORGANISM(S): Mus musculus

PROVIDER: GSE311122 | GEO | 2026/01/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cortical astrocytic neogenin, a key protein switching HIF1/2ɑ-VEGFa-induced angiogenesis to MEGF10-driven phagocytosis

Project description:Cortical astrocytic neogenin, a key protein switching HIF1/2ɑ-VEGFa-induced angiogenesis to MEGF10-driven phagocytosis

| PRJNA1368708 | ENA

Astrocytic Sox9 preserves cognitive function in models of Alsheimer's Disease [RNA-Seq]

Project description:Astrocytes play essential roles in the brain and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, our knowledge of how astrocytes contribute to disease pathogenesis is incomplete, accordingly harnessing their biology towards therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer’s Disease (AD) models. We found that Sox9 overexpression in astrocytes in AD models clears existing amyloid beta (Aβ) plaques and preserves cognitive function. Mechanistically, Sox9 promotes the phagocytosis of Aβ plaques by astrocytes through the regulation of the phagocytic receptor MEGF10, which is sufficient to preserve cognitive function in AD models. Collectively, these studies highlight new roles for astrocytic Sox9 during aging and AD, while identifying Sox9-MEGF10 signaling as a prospective astrocyte-based therapeutic approach to ameliorate cognitive decline in neurodegenerative disease.

2026-01-06 | GSE294900 | GEO

Astrocytic Sox9 preserves cognitive function in models of Alsheimer's Disease

2026-01-06 | GSE294933 | GEO

Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5+ mouse long-term hematopoietic stem cells

Project description:Hematopoietic stem cells (HSCs) self-renew and generate all blood cells. Recent studies with single-cell transplants and lineage tracing suggest that adult HSCs are diverse in their reconstitution and lineage potentials. However, prospective isolation of these subpopulations has remained challenging. Here, we identify Neogenin-1 (NEO1) as a unique surface marker on a fraction of mouse HSCs labeled with Hoxb5, a specific reporter of long-term HSCs (LT-HSCs). We show that NEO1+Hoxb5+ LT-HSCs expand with age and respond to myeloablative stress in young mice, while NEO1–Hoxb5+ LT-HSCs exhibit no significant change in number. Furthermore, NEO1+Hoxb5+ LT-HSCs are more often in the G2/S cell cycle phase compared to NEO1–Hoxb5+ LT-HSCs in both young and old bone marrow. Upon serial transplantation, NEO1+Hoxb5+ LT-HSCs exhibit myeloid-biased differentiation and reduced reconstitution, while NEO1–Hoxb5+ LT-HSCs are lineage-balanced and stably reconstitute recipients. Gene expression analysis reveals erythroid and myeloid priming in the NEO1+ fraction and association of quiescence and self-renewal-related transcription factors with NEO1− LT-HSCs. Finally, transplanted NEO1+Hoxb5+ LT-HSCs rarely generate NEO1–Hoxb5+ LT-HSCs, while NEO1–Hoxb5+ LT-HSCs repopulate both LT-HSC fractions. This supports a model in which dormant, balanced, NEO1–Hoxb5+ LT-HSCs can hierarchically precede active, myeloid-biased NEO1+Hoxb5+ LT-HSCs.

2019-11-10 | GSE130504 | GEO

Cellular and molecular alterations to muscles and neuromuscular synapses in Megf10-related myopathy

Project description:Loss-of-function mutations in MEGF10 lead to a rare and understudied neuromuscular disorder known as MEGF10-related myopathy. There are no treatments for the progressive respiratory distress, motor impairment, and structural abnormalities in muscles caused by the loss of MEGF10 function. In this study, we asked whether mice lacking MEGF10 (MEGF10 KO) could be used as a model to generate preclinical insights to treat MEGF10-related myopathy. We deployed cellular and molecular assays to examine juvenile, young adult, and middle-aged Megf10 constitutive knockout (KO) mice. We found fewer muscle fibers in developing and adult Megf10 KO mice, supporting published studies that MEGF10 regulates myogenesis by affecting satellite cell differentiation. Interestingly, muscle fibers do not exhibit morphological hallmarks of atrophy in either young adult or middle-aged Megf10 KO mice. We next examined the neuromuscular junction (NMJ), in which MEGF10 has been shown to concentrate postnatally, using light and electron microscopy. We found early and progressive degenerative features at the NMJs of Megf10 KO mice. These include increased postsynaptic fragmentation, axon terminals failing to completely appose the postsynaptic region and perisynaptic Schwann cells intruding into the NMJ synaptic cleft. These findings strongly suggest that the NMJ is a site of postnatal pathology in MEGF10-related myopathy. We next sought to identify molecular mechanisms altered in muscles lacking Megf10 using RNA-seq. We discovered genes and pathways associated with myogenesis, skeletal muscle health, and NMJ stability dysregulated in Megf10 KO mice compared to wild-type mice. Altogether, these data support using MEGF10 KO mice to discover and test potential treatments for MEGF10-related myopathy.

2024-02-20 | GSE256199 | GEO

RNA seq of CD45.2+ Neo1 deficient or wildtype Hematopoietic stem cells, 4 or 15 month after stem cell transplantation

Project description:To study the role of the receptor Neo1 in Hematopoietic stem cells (HSC) we transplanted Neo1 deficient bone marrow and wildtype controls on a CD45.2 background into lethally irradiated CD45.1 recipients. Either 4 or 15 months after transplantation we isolated HSC (Lineage -, Sca-1+, c-Kit+, Cd150+, CD48-, CD34-, CD45.2+) to identify molecular differences due to Neo1 deficiency and found a loss of HSC quiescence and signatures associated with decreased stem cell function.

2020-07-22 | E-MTAB-7902 | biostudies-arrayexpress

Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch (ChIP-Seq)

Project description:Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression, and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrogenic programs while inhibiting Stat3-mediated astrogliogenesis, and thereby regulate phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision. Examination of Hdac3 and p300 genomewide occupancy in differentiating oligodendrocytes

2016-02-21 | E-GEOD-76411 | biostudies-arrayexpress

Transcription factors enriched in tumor-associated enhancers in VHL-deficient ccRCC

Project description:VHL loss is the most common genetic alteration event in ccRCC. We profiled histone modifications from VHL-deficient ccRCC primary tumors and cell lines. We show that ccRCCs exhibit a pervasive gain of enhancers around hypoxic and metabolic transcriptional targets. Motif analysis using HOMER revealed significant enrichment of AP-1, ETS, NFĸB and HIFα in tumor enhancers. We generated ChIP-seq binding data for c-Jun, ETS1, NFĸB, and P300, a histone acetyltransferase, in 786-O cells. ChIP-seq profiles of HIF2α and HIF1β in 786-O were already generated previously (GSE34871)

2017-08-22 | GSE86092 | GEO

Stress induces behavioral abnormalities by increasing expression of phagocytic receptor MERTK in astrocytes to promote synapse phagocytosis

Project description:Early life stress such as childhood abues and childhood neglect has been frequently implicated in evoking mental disorders later in life. However, it is not well understood what is the underlying mechanism between early life stress and mental disorders. Our in vitro, in vivo and brain organoid experiments revealed that stress hormones increase Mertk expression in astrocytes through glucocorticoid receptor (GR). Furthermore, early life stress (ESD) exposure significantly incrased astrocyte-mediated synapse phagocytosis via GR/MERTK pathway in various brain regions including somatosensory cortex and orbitofrontal cortex. In those brain regions, the excitatory postsynaptic density was remarkably decreased with an increase in astrocytic phagocytosis of excitatory postsynapses. Importantly, ablating GR or MERTK in astrocytes prevented ESD-induced loss of excitatory snapses, abnormal neural activities and behavioral deficits. Taken together, this study revelas a new role of astrocytic GR/MERTK pathway in evoking stress-induced abnormal behaviors in mice, suggesting astrocytic GR/MERTK signaling could be a potential therapeutic target for stress-induced mental disorders.

2023-08-22 | GSE234945 | GEO

Yuan- microRNAs upregulated in Ep300-overexpressing mouse heart

Project description:Objective: To characterize downstream effectors of p300 acetyltransferase in the myocardium. Background: Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known. Methods and Results: Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression. Chromatin immunoprecipitation demonstrated binding of p300 to the enhancers of the angiogenic regulators Angpt1 and Egln3. Interestingly, p300 overexpression in vivo was also associated with relative upregulation of several members of the anti-angiogenic miR-17~92 cluster in vivo. Confirming this finding, both miR-17-3p and miR-20a were upregulated in neonatal rat ventricular myocytes following adenoviral transduction of p300. Relative expression of most members of the 17~92 cluster was similar in all 4 cardiac chambers and in other organs, however, significant downregulation of miR-17-3p and miR-20a occurred between 1 and 8 months of age in both wt and tg mice. The decline in expression of these microRNAs was associated with increased expression of VEGFA, a validated miR-20a target. In addition, miR-20a was demonstrated to directly repress p300 expression through a consensus binding site in the p300 3’UTR. In vivo transduction of p300 resulted in repression both of p300 and of p300-induced angiogenic transcripts. Conclusion: p300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a. 4 littermates, 3 transgene-expressing and 1 wild-type were analyzed. Samples were spotted in duplicate.

2013-09-30 | E-GEOD-50843 | biostudies-arrayexpress

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