Human cerebral organoids model tumor initiation and infiltration in an autologous astrocyte-supported setting [RNA-Seq]
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PROVIDER: PRJNA1284666 | ENA |
REPOSITORIES: ENA
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Project description:Human cerebral organoids model tumor initiation and infiltration in an autologous astrocyte-supported setting [snRNA-seq]
| PRJNA1284667 | ENA
Project description:Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing c-MYC, a common oncogene in brain tumors. GFP+/c-MYChigh cells were isolated from tumor organoids and used in two different approaches: GFP+/c-MYChigh cells co-cultured with cerebral organoid slices or fused as spheres to whole organoids. GFP+/c-MYChigh cells used in both approaches exhibited tumor-like properties, including an immature phenotype and a highly proliferative and invasive potential. We demonstrate that the latter is influenced by astrocytes supporting the GFP+/c-MYChigh cells while X-ray irradiation significantly kills and impairs tissue infiltration of GFP+/c-MYChigh cells. In summary, the model represents major features of tumorous and adjacent normal tissue and may be used to evaluate appropriate cancer treatments.
2025-07-01 | GSE301277 | GEO
Project description:Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing c-MYC, a common oncogene in brain tumors. GFP+/c-MYChigh cells were isolated from tumor organoids and used in two different approaches: GFP+/c-MYChigh cells co-cultured with cerebral organoid slices or fused as spheres to whole organoids. GFP+/c-MYChigh cells used in both approaches exhibited tumor-like properties, including an immature phenotype and a highly proliferative and invasive potential. We demonstrate that the latter is influenced by astrocytes supporting the GFP+/c-MYChigh cells while X-ray irradiation significantly kills and impairs tissue infiltration of GFP+/c-MYChigh cells. In summary, the model represents major features of tumorous and adjacent normal tissue and may be used to evaluate appropriate cancer treatments.
2025-07-01 | GSE301276 | GEO
Project description:Early-passage (<10 passages) cultures of melanoma cells from metastatic lymph node lesions and normal adult melanocytes explanted in parallel from the adjacent, non-involved skin of 5 patients were compared by cDNA arrays. Differences between normal and neoplastic counterparts were then assessed upon adjustment for individual factors. cDNA expression profiles comparison between normal and neoplastic counterparts in a strictly autologous setting
2012-09-28 | E-GEOD-38312 | biostudies-arrayexpress
Project description:Primary human cells cultured in 3D organoid format have great promise as potential regenerative cellular therapies, but their immunogenicity has not yet been fully characterized. In this study, we use in vitro co-cultures and in vivo humanized mouse experimental models to examine the human immune response to autologous and allogeneic primary cholangiocyte organoids (PCOs). Our data demonstrate that PCOs upregulate the expression of HLA-I and HLA-II in inflammatory conditions. The immune response to allogeneic PCOs is driven by both HLA-I and HLA-II and is substantially ameliorated by donor-recipient HLA matching. Autologous PCOs induce a low-level immune infiltration into the graft site, while allogeneic cells display evolving stages of immune rejection in vivo. Our findings have important implications for the design and clinical translation of autologous and allogeneic organoid cellular therapies.
2024-01-20 | GSE253679 | GEO
Project description:This study investigated the role of astrocyte-derived EVs in neuroprotection and tissue recovery post-ischemia. Cortical astrocytes were cultured under normoxic and hypoxic conditions to harvest extracellular vesicles (EVs). The EVs were then administered to rats that had undergone experimental stroke. We assessed infarct volume, neuronal survival, and neurological function, and utilized label-free mass spectrometry-based proteomics to evaluate the hypoxia-induced changes in the EV proteome. Administration of astrocyte-derived EVs significantly reduced infarct volume, improved neurological function, and mitigated blood-brain barrier (BBB) permeability. Proteomic analysis revealed a differential expression of 67 upregulated proteins under hypoxic conditions and 37 downregulated proteins under normoxic conditions, highlighting the protective protein signatures elicited by astrocytes. Our findings underscore the role of astrocyte-derived EVs in fostering a conducive environment for neuronal survival under hypoxic stress. (Supported by DGAPA-PAPIIT IN207020 and IN214723 and CONACYT A1-S-13219).
2025-06-14 | PXD050160 | Pride
Project description:The aim of the study was to investigate the effects of autologous equine serum (AES) incubated for 24 h and autologous conditioned serum (ACS) on inflamed equine chondrocyte pellets in vitro.
2023-04-19 | GSE152253 | GEO
Project description:Chromosomes and genes are non-randomly arranged within the mammalian cell nucleus. Clustering of genes is of great significance in transcriptional regulation. However, the relevance of gene clustering in their expression during differentiation of neural precursor cells (NPCs) into astrocytes remains unclear. We performed a genome-wide enhanced circular chromosomal conformation capture (e4C) to screen genes associated with an astrocyte-specific gene, glial fibrillary acidic protein (Gfap), during astrocyte differentiation. We identified 13 genes that were specifically associated with Gfap and expressed in NPC-derived astrocytes. These results provide evidence for functional significance of gene clustering in transcriptional regulation during NPCs differentiation. comparison of NPCs vs LIF+ vs LIF- cells.
2015-02-20 | E-GEOD-66097 | biostudies-arrayexpress
Project description:The intrinsic mechanisms that regulate neurotoxic versus neuroprotective astrocyte phenotypes and their effects on central nervous system (CNS) degeneration and repair remain poorly understood. Here, we show injured white matter astrocytes differentiate into two distinct C3-positive and C3-negative reactive populations, previously simplified as neurotoxic (A1) and neuroprotective (A2)1,2, which can be further subdivided into unique subpopulations defined by proliferation and differential gene expression signatures. We find the balance of neurotoxic versus neuroprotective astrocytes is regulated by discrete pools of compartmented cAMP derived from soluble adenylyl cyclase (sAC) and show proliferating neuroprotective astrocytes inhibit microglial activation and downstream neurotoxic astrocyte differentiation to promote retinal ganglion cell (RGC) survival. Finally, we report a new, therapeutically tractable viral vector to specifically target optic nerve head astrocytes and show elevating nuclear or depleting cytoplasmic cAMP in reactive astrocytes inhibits deleterious immune cell infiltration and promotes RGC survival after optic nerve injury. Thus, soluble adenylyl cyclase and compartmented, nuclear- and cytoplasmic-localized cAMP in reactive astrocytes act as a molecular switch for neuroprotective astrocyte reactivity that can be targeted to inhibit microglial activation and neurotoxic astrocyte differentiation to therapeutic effect. These data expand upon and define new reactive astrocyte subtypes and represents a novel step towards the development of gliotherapeutics for the treatment of glaucoma and other optic neuropathies.
2023-12-11 | GSE245816 | GEO
Project description:Inflammation features in diverse central nervous system disorders such as stroke, trauma, neurodegeneration, infection and autoimmunity. To better understand how inflammatory mediators may alter astrocyte functions, we examined the effects of transforming growth factor-β1 (TGF-β1), lipopolysaccharide (LPS) and interferon-gamma (IFNγ) on purified, murine, primary cortical astrocyte cultures. We used microarrays to conduct whole genome expression profiling, and measured calcium signaling, which is implicated in mediating dynamic astrocyte functions. Combinatorial exposure to TGF-β1, LPS and IFNγ significantly modulated astrocyte expression of over 6,800 genes and resulted in both additive and synergistic changes compared with individual stimuli alone. Bioinformatic analysis revealed that combinatorial treatment significantly and markedly up regulated molecular networks and pathways associated with immune signaling and with regulation of cell compromise, death, growth and proliferation. These findings provide databases of astrocyte transcriptome changes elicited by the inflammatory stimuli, TGF-β1, LPS and IFNγ alone and in combination, and show that these stimuli up regulate astrocyte molecular networks associated with immune- and injury-related functions and significantly alter astrocyte calcium signaling evoked by multiple GPCR. We used microarrays to examine the effects of transforming growth factor-β1 (TGF-β1), lipopolysaccharide (LPS) and interferon-gamma (IFNγ) on purified, murine, primary cortical astrocyte cultures.
2012-10-18 | E-GEOD-36089 | biostudies-arrayexpress