Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuro-immune organoid model reveals a role of microglia in cell stress response and emergence of neural activity

ABSTRACT: Purpose: Many fundamental questions about microglia diversity and function during development remain unanswered as we lack experimental strategies to interrogate their interactions with other cell types and responses to perturbations ex vivo. Methods: By using 10X Genomics scRNAseq, we generated transcriptomic data across different microglia models. Additionally, we performed microglia engraftment into cortical brain organoids and analyzed molecular changes in different cell types occurring in response to the presence of microglia. Results: We compared human microglia states across culture models, including cultured primary microglia and pluripotent stem cell-derived microglia and developed a ‘report card’ of gene expression signatures differentially recruited and attenuated across these distinct experimental models.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180945 | GEO | 2021/07/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Neuro-immune organoid model reveals a role of microglia in cell stress response and emergence of neural activity

Project description:Neuro-immune organoid model reveals a role of microglia in cell stress response and emergence of neural activity

| PRJNA750089 | ENA

RNA-seq of mouse brain tissue repopulating microglia in response to traumatic brain injury

Project description:We assessed the roles of repopulating microglia in brain repair using mouse models. In this project, we show that removal of microglia from the mouse brain has little impact on the outcome of TBI but inducing the turnover of these cells through either pharmacologic or genetic approaches can yield a neuroprotective microglial phenotype that profoundly aids recovery. As a part of the experimental approaches, we perform bulk RNA sequencing experiments to unbiasedly profile the transcriptome of repopulating microglia. We identified unique gene signatures from repopulating microglia cells and infer how these cells modulate the microenvironment after TBI.

2020-02-15 | E-MTAB-8765 | biostudies-arrayexpress

Chemically Induced Paneth Cells Provide Superior In Vivo Mimic to Organoid-derived Analog

Project description:Paneth cells (PCs) are post-mitotic secretory cells of the small intestine that produce antimicrobials, growth factors, and cytokines. Multiple diseases have been linked to alterations in PC function. Past studies of PCs have relied on in vivo models, and limited in vitro models, including organoids. While useful, whether the in vitro models recapitulate in vivo biology is an important, yet unanswered question. Here, we present a bona fide in vitro PC-enriched population derived via chemically-induced (CI) differentiation of primary murine adult stem cells. We define the identity of PCs in our system and compare to PCs of established organoid systems and those found in vivo. Importantly, we demonstrate stimulant-induced and microbe-responsive antimicrobial function of our CI-PCs – hallmark functions of PCs in vivo. Thus, we define and produce the most physiologically-relevant in vitro PC population to date, providing a superior tool to study cellular development, host-microbe interactions, and inflammatory disease.

2018-04-02 | GSE100274 | GEO

High-throughput characterization of hematopoietic stem cell engraftment after intravenous and intracerebroventricular dosing

Project description:Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) has shown clear neurological benefit in rare diseases, which is achieved through the engraftment of genetically modified microglia-like cells (MLCs) in the brain. Still, the engraftment dynamics and the nature of engineered MLCs, as well as their potential use in common neurogenerative diseases have remained largely unexplored. Here, we firstly comprehensively characterized how different routes of administration affect the biodistribution of genetically engineered MLCs and other HSPC-derivatives in mice. We then generated a high-resolution single cell transcriptional map of MLCs and discovered that they could clearly be distinguished from macrophages as well as from resident microglia by the expression of a specific gene signature which is reflective of their HSPC ontogeny and irrespective of their long-term engraftment history. Lastly, using murine models of Parkinson’s disease and frontotemporal dementia, we demonstrated that MLCs can deliver therapeutically relevant levels of protein to the brain, thereby opening avenues for the clinical translation of HSPC-GT to the treatment of major neurological diseases.

2022-05-31 | GSE201756 | GEO

Expression data from polarized adult human microglia

Project description:Myeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or “polarization” and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS). We used Affymetrix Human Gene HT 2.0 microarrays to compare whole transcriptomes of microglia and macrophages under defined polarization conditions.

2016-02-01 | GSE76734 | GEO

Expression data from polarized adult human macrophages

2016-02-01 | GSE76736 | GEO

Transcription profiling by array of human Acute Lymphobastic Leukemia xenografts in mouse to validate the mouse model

Project description:Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential.Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation.We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

2010-04-26 | E-MEXP-2648 | biostudies-arrayexpress

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia [GFP]

Project description:Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.

2018-04-07 | GSE108569 | GEO

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia [LPS]

2018-04-07 | GSE108575 | GEO

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia

2018-04-07 | GSE84819 | GEO