Revisiting neurogenesis in the adult human brain cortex
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ABSTRACT:
PROVIDER: PRJNA765321 | ENA |
REPOSITORIES: ENA
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Project description:Neural stem cells (NSCs) generating new neurons are restricted to few niches in the adult mammalian brain, while the remainder rather promotes gliogenesis. Here we take advantage of the spatial separation of an NSC niche (the subependymal zone) and the region to where the newly generated neurons migrate and integrate (the olfactory bulb). Using state-of-the-art mass spectrometry we present a comprehensive proteomic characterization of these niches compared to a region of the normal brain parenchyma (cerebral cortex) that is not contusive to neurogenesis and new neuron integration. We find unique compositions of regulatory ECM components in the neurogenic niche, with quiescent NSCs as a main source of their local ECM, including the multi-functional enzyme transglutaminase 2 that we identify as crucial for neurogenesis. Atomic force microscopy further corroborates indications from the proteome that neurogenic niches are significantly stiffer than the non-neurogenic parenchyma, highlighting the unique properties of these special niches.
2020-01-27 | PXD016632 | Pride
Project description:Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.
2019-11-12 | PXD009845 | Pride
Project description:The epigenetic mechanisms that enable lifelong neurogenesis from neural stem cells (NSCs) in the adult mammalian brain are poorly understood. Here we show that JMJD3, a histone H3-lysine 27 (H3K27) demethylase, acts as a critical activator of neurogenesis. 3 biological replicates of JMJD3 null (P9 UBC-Cre/ERT2;Jmjd3F/F) and 3 biological replicates of littermate controls were used to analyze the effect of JMJD3 deletion on gene expression.
2014-07-30 | E-GEOD-59888 | biostudies-arrayexpress
Project description:The epigenetic mechanisms that enable lifelong neurogenesis from neural stem cells (NSCs) in the adult mammalian brain are poorly understood. Here we show that JMJD3, a histone H3-lysine 27 (H3K27) demethylase, acts as a critical activator of neurogenesis.
2014-07-30 | GSE59888 | GEO
Project description:Spatial transcriptomics analysis of adult hippocampal neurogenesis in the human brain
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Project description:Adult hippocampal neurogenesis (AHN) has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in post-mortem human hippocampal samples by combining spatial transcriptomics and fluorescent in situ hybridization. We detected very few cells expressing neural stem cell- and proliferation-specific genes in the human dentate gyrus (DG) from childhood to middle age, suggesting very low levels of hippocampal neurogenesis throughout life. However, we observed at all ages a significant number of DG cells expressing the immature neuronal marker DCX. The majority of DCX+ cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature. Overall, our study investigates for the first time the extent of AHN in the human brain with spatial transcriptomic tools and reveals important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus.
2024-10-16 | GSE248545 | GEO
Project description:Purpose:To gain a deeper insight into how TCF20 regulates neurogenesis in mice brain, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by TCF20 deletion at E13.5. Methods: Total RNA was extracted from E13.5 telencephalic tissue of TCF20 WT HET KO mice. Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina HiSeq 2500 platform in Annoroad Genomics. Results: Approximately approximately one thousand transcripts showed differential expression between the WT and TCF20 KO brain cortex, with a fold change ≥1.5 and p value <0.05. Gene ontology (GO) analysis showed that the down-regulated genes were enriched in the terms related to neurogenesis, neuronal specification, neural differentiation and secretion by cells. Up-regulated genes showed a significant enrichment of terms involved in up regulation of hypersensitivity and up regulation of inflammatory response. These results reflected the importance of TCF20 in cortical neurogenesis. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding how TCF20 gene contribute to brain cortical development.
2019-08-08 | GSE135483 | GEO
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Project description:Analysis of steady-state mRNA levels in adult mouse brain cortex at week 17-18 from wild-type C57BL/6J, Dp16, and interferon receptor dosage-normalized Dp16^2xIFNRs mice.
2024-07-18 | GSE272568 | GEO