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Microglia-derived IGF1 promotes neurogenesis of GABaergic neurons in perinatal human brain [MGEorganoid_scRNAseq]

ABSTRACT: Microglia-derived IGF1 promotes neurogenesis of GABaergic neurons in perinatal human brain [MGEorganoid_scRNAseq]

PROVIDER: PRJNA1148140 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR30245969.fastq.gz	Fastqsanger.gz
	SRR30245970.fastq.gz	Fastqsanger.gz
	SRR30245972.fastq.gz	Fastqsanger.gz
	SRR30245973_1.fastq.gz	Fastqsanger.gz

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Microglia-derived IGF1 promotes neurogenesis of GABaergic neurons in perinatal human brain

Project description:Microglia-derived IGF1 promotes neurogenesis of GABaergic neurons in perinatal human brain

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Microglia-derived IGF1 promotes neurogenesis of GABaergic neurons in perinatal human brain [MGEorganoid_scRNAseq]

Project description:We conducted scRNAseq to investigate the transcriptomics of induced microglia (iMG) and iMG containing MGE-oriented organoids.

2025-06-18 | GSE274829 | GEO

Microglia-derived IGF1 promotes neurogenesis of GABaergic neurons in perinatal human brain

Project description:We conducted snRNAseq to investigate the transcriptomics of postmortem prenatal and peirnatal human brains.

2025-06-18 | GSE296073 | GEO

Microglia actively remodels adult hippocampal neurogenesis through the phagocytosis secretome

Project description:During adult hippocampal neurogenesis, the majority of newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia in order to avoid disturbing the surrounding neurons. Here, we propose that phagocytosis is not merely a passive process of corpse removal but has an active role in maintaining adult hippocampal neurogenesis. First, we found that neurogenesis was disrupted in three defective microglial phagocytosis KO models in vivo (P2Y12, MerTK/Axl , GPR34). We then followed an in vitro approach to perform a transcriptomic analysis of microglial phagocytosis and identified genes involved in metabolism, chromatin remodeling, and neurogenesis-related functions. Finally, we determined that the phagocytic microglia secretome limits the production of new neurons both in vivo and in vitro. Our data suggest that reprogrammed phagocytic microglia acts as a sensor of local cell death, modulating the balance between cell proliferation and cell survival in the neurogenic niche, supporting the long-term maintenance of adult hippocampal neurogenesis.

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Delayed maturation of Fragile X Syndrome GABAergic neurogenesis revealed by functional and single-cell gene expression analysis

Project description:FXS (Fragile X Syndrome), a leading monogenic cause of intellectual disability and autism spectrum disorder, is caused by an expansion of a CGG repeat in the 5′-UTR of the FMR1 (Fragile X Mental Retardation-1) gene. While current studies of FXS have focused on the effects of Fragile X Mental Retardation Protein (FMRP) loss in excitatory neurons, evidence suggests that GABAergic inhibitory networks are also affected in FXS. In this study, we developed a method to reproducibly derive GABAergic inhibitory neurons from multiple FXS and control human pluripotent stem cell lines (PSCs). We found that compared to control, functional assays with microelectrode arrays and immunocytochemistry suggested a developmental delay in the maturing FXS inhibitory network that involves the GABA function switch. The GABA function switch converts the GABAA channel’s role from depolarization to hyperpolarization and has profound effects on the developing brain. To investigate the cause of this delay, we analyzed 14,400 single-cell transcriptomes from FXS and control PSC-derived GABAergic neuron cultures at early and late stages of neurogenesis. Genes related to neuroblast proliferation were upregulated in FXS cells, while neuron-specific differentially expressed genes (DEGs) associated with action potential regulation, synaptic processes, and mitochondria function were downregulated in FXS cells. In addition, autism-associated genes were overrepresented in the DEGs. Our analysis of inhibitory neuron development suggests that loss of FMRP is associated with delays in the GABAergic neurogenesis and maturation. This observation suggests a novel direction for understanding the underlying disease mechanisms and may help to guide development of therapeutic interventions.

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Combinatorial transcription factor binding encodes cis-regulatory wiring of forebrain GABAergic neurogenesis

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Expression data from E18.5 Igf1 -/- (homozygous mutant) and Igf1+/+ (normal wild type control) mouse lungs

Project description:Insight into the role of Insulin-like Growth Factor (IGF) in development of lungs has come from the study of genetically modified mice. IGF1 is a key factor during lung development. IGF1 deficiency in the neonatal mouse causes respiratory failure collapsed alveoli and altered alveolar septa. To further characterize IGF1 function during lung development we analyzed Igf1-/- mouse prenatal lungs in a C57Bl/6 genetic background. Mutant lungs showed disproportional hypoplasia, disorganized extracellular matrix and dilated alveolar capillaries. IGF1 target genes during lung maturation were identified by analyzing RNA differential expression in Igf1-/- lungs using microarrays. Lungs from E18.5 were isolated from both Igf1+/+ wild type and Igf1-/- null mice and pooled to obtain RNA. Heterozygous male and female with a genetic background C57BL/6J were mated to obtain embryos at embrionic (E) stage 18.5 days post coitum (E18.5). 3 biological replicates per genotype.

2014-03-31 | E-GEOD-17157 | biostudies-arrayexpress

Combinatorial transcription factor binding encodes cis-regulatory wiring of forebrain GABAergic neurogenesis

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2023-09-11 | GSE222183 | GEO

Microglia actively remodels adult hippocampal neurogenesis through the phagocytosis secretome

Project description:Microglia actively remodels adult hippocampal neurogenesis through the phagocytosis secretome

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Expression data from E18.5 Igf1 -/- (homozygous mutant) and Igf1+/+ (normal wild type control) mouse lungs

2014-03-31 | GSE17157 | GEO