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Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain [Bulk RNAseq]

ABSTRACT: iPSC derived microglial precursors were transplanted into the brains of neonatal mice, FACS sorted out based on GFP+ following 2 months, and compared to in vitro differentiated iPSC derived microglia from the same precursors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139192 | GEO | 2019/11/27

REPOSITORIES: GEO

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Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain [Single Cell RNAseq]

Project description:iPSC derived microglial precursors were tranplanted into the brains of neonatal mice, FACS sorted out based on GFP+ following 2 months, and compared to in vitro differentiated iPSC derived microglia from the same precursors.

2019-11-27 | GSE139193 | GEO

Development of a chimeric model to study and manipulate human microglia in vivo (bulk RNA-seq dataset)

Project description:iPSC-derived microglia offer a powerful tool to study microglial homeostasis and disease-associated inflammatory responses. Yet, microglia are highly sensitive to their environment, exhibiting transcriptomic deficiencies when kept in isolation from the brain. Furthermore, species-specific genetic variations demonstrate that rodent microglia fail to fully recapitulate the human condition. To address this, we developed an approach to study human microglia within a surrogate brain environment. Transplantation of iPSC-derived hematopoietic-progenitors into the postnatal brain of humanized, immune-deficient mice results in context-dependent differentiation into microglia and other CNS macrophages, acquisition of an ex vivo human microglial gene signature, and responsiveness to both acute and chronic insults. Most notably, transplanted microglia exhibit robust transcriptional responses to Ab-plaques that only partially overlap with that of murine microglia, revealing new, human-specific Ab-responsive genes. We therefore have demonstrated that this chimeric model provides a powerful new system to examine the in vivo function of patient-derived and genetically-modified microglia.

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iPSC-derived microglia carrying the TREM2 R47H/+ mutation are pro-inflammatory and promote synapse loss.

Project description:Genetic findings have highlighted key roles for microglia in the pathology of neurodegenerative conditions such as Alzheimer’s disease (AD). A number of mutations in the microglial protein TREM2 (triggering receptor expressed on myeloid cells 2) have been associated with increased risk for developing Alzheimer’s disease (AD), most notably the R47H/+ substitution. We employed gene editing and stem cell models to gain insight into the effects of the TREM2 R47H/+ mutation on human iPSC-derived microglia. We found transcriptional changes affecting numerous cellular processes, with R47H/+ cells exhibiting a pro-inflammatory gene expression signature. TREM2 R47H/+ also caused impairments in microglial movement and the uptake of multiple substrates, as well as rendering microglia hyper-responsive to inflammatory stimuli. We developed an in vitro laser-induced injury model in neuron-microglia co-cultures, finding an impaired injury response by TREM2 R47H/+ microglia. Furthermore, mouse brains transplanted with TREM2 R47H/+ microglia exhibited reduced synaptic density, with upregulation of multiple complement cascade components in TREM2 R47H/+ microglia suggesting inappropriate synaptic pruning as one potential mechanism. These findings identify a number of potentially detrimental effects of the TREM2 R47H/+ mutation on microglial gene expression and function likely to underlie its association with AD.

2024-03-06 | GSE241858 | GEO

Transcription profiling of neonatal rat microglia after IFN-gamma activation

Project description:IFN-gamma is a classical microglial stimulant. We used microarrays to investigate the microglial gene regulatory network activated by interferon-gamma. Experiment Overall Design: Primary rat microglia cultures were established and maintained for 15 days. For activation studies, fresh media containing IFN-gamma (100 U/ml) were added and left overnight (16 hours). Total RNA was extraction and hybridized on Affymetrix microarrays (RG_U34A). Five arrays were run from total RNA derived from unstimulated 5 independent cultures (Mgl_CON1, Mgl_CON2, Mgl_CON3, Mgl_CON5 and Mgl_CON6). Three standard microglial cultures were stimulated (Mgl_IFNgamma_2 and Mgl_IFNgamma_3) with one of the samples analysed in triplicate as a technical control (Mgl_IFNgamma_1a, Mgl_IFNgamma_1b and Mgl_IFNgamma_1c).

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Functional Mature Human Microglia Developed in Human iPSC Microglial Chimeric Mouse Brain

Project description:Microglia, the brain-resident macrophages, exhibit highly dynamic functions in neurodevelopment and neurodegeneration. Human microglia possess unique features as compared to mouse microglia, but our understanding of human microglial functions is largely limited by an inability to obtain human microglia under homeostatic states. We developed a human pluripotent stem cell (hPSC)-based microglial chimeric mouse brain model by transplanting hPSC-derived primitive macrophage precursors into neonatal mouse brains. The engrafted human microglia widely disperse in the brain and replace mouse microglia in corpus callosum at 6 months post-transplantation. Single-cell RNA-sequencing of the microglial chimeric mouse brains reveals that xenografted hPSC-derived microglia largely retain human microglial identity, as they exhibit signature gene expression patterns consistent with physiological human microglia and recapitulate heterogeneity of adult human microglia. Importantly, the engrafted hPSC-derived microglia exhibit dynamic response to cuprizone-induced demyelination and species-specific transcriptomic differences in the expression of neurological disease-risk genes in microglia. This model will serve as a novel tool to study the role of human microglia in brain development and degeneration.

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Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain [Bulk RNAseq]

Project description:Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain [Bulk RNAseq]

| PRJNA578732 | ENA

Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain.

Project description: Not available

| S-EPMC6911218 | biostudies-literature

Gene expression data from human iPSC differentiated to macrophages and microglia, compared to human blood-derived monocytes and human primary fetal microglia

Project description:A human Pluripotent Stem Cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response Walther Haenseler, Stephen N. Sansom, Julian Buchrieser, Sarah E. Newey, Craig S. Moore, Francesca J. Nicholls, Satyan Chintawar, Christian Schnell, Jack P. Antel, Nicholas D. Allen, M. Zameel Cader, Richard Wade-Martins, William S. James, Sally A. Cowley The aim of the experiment was to compare the gene expression profiles from human iPSC-derived embryonic macrophages (both precursors, mature, and cells cultured in 'microglia medium'), with iPSC-macrophages differentiated to microglia by co-culture with iPSC-derived cortical neurons. They were also compared to human blood-derived monocytes and to human primary fetal microglia.

2016-11-14 | GSE89795 | GEO

Expressoin data from iPSC with different cell of origin

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