RNA-Seq analysis of mouse neural stem cells with or wihtout Rad21 knockdown.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE225608 | GEO | 2024/02/20
REPOSITORIES: GEO
Similar Datasets
Project description:The activation of quiescent neural stem cells (qNSCs) in the dentate gyrus is required for lifelong neurogenesis. However, the mechanisms that promote the exit of neural stem cells (NSCs) from quiescence remain elusive. We demonstrate that the expression of plant homeodomain finger protein 2 (Phf2) activates the exit of postnatal mouse NSC from shallow quiescence. Loss of Phf2 prevents NSC activation and neurogenesis in postnatal 30 (P30) mice but does not decrease the label-retaining NSC pool, indicating that Phf2 is not required for the exit of NSC from quiescence. NSC-specific deletion of Phf2 modestly compromises embryonic mouse NSC proliferation without increasing apoptosis, indicating that Phf2 is crucial for embryonic development. Moreover, human cortical organoids reveal that Phf2 promotes NPC proliferation via a lysine demethylase-independent manner. Mechanistically, Phf2 directly binds to the cohesion complex via Rad21 and regulates the DNA replication in mouse NSC by associating with the cohesion complex releasing protein Wapl activity. Our study identifies the Phf2-cohesin complex mediated DNA replication for neural stem cell activation in a lysine demethylase-independent manner.
2024-03-01 | PXD040515 | JPOST Repository
Project description:The precise regulation of neural stem cell quiescence and activation is crucial for normal brain development and lifelong nwurogenesis. However, the mechanisms that control neural stem cell activation remains poorly understood. In this study, we investigate the role of Phf2 in this process.
2024-02-14 | GSE225438 | GEO
Project description:Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilise during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this reduction in stem cell depletion rate in young adults is the result of coordinated changes in stem cell behaviour. In particular, while proliferating neural stem cells in juveniles differentiate rapidly, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomic, modelling and label-retention analyses indicate that resting cells have a higher activation rate and greater contribution to neurogenesis than dormant cells, which have not left quiescence. These progressive changes in stem cell behaviour result from reduced expression of the pro-activation protein ASCL1 due to increased post-translational degradation. These cellular mechanisms help reconcile current contradictory models of hippocampal NSC dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species including humans.
2020-12-15 | GSE159768 | GEO
Project description:Experience governs neurogenesis from radial-glial neural stem cells (RGLs) in the adult hippocampus to support memory. Transcription factors in RGLs integrate physiological signals to dictate quiescence-activation decisions and self-renewal divisions. Whereas asymmetric RGL self-renewal drives neurogenesis during favorable conditions, symmetric divisions prevent premature neurogenesis during unfavorable conditions while amplifying RGLs to anticipate neurogenic demands when conditions become favorable. Here, we show that the transcription factor Kruppel-like factor 9 (Klf9) is enriched in quiescent RGLs and inducible, bidirectional modulation of Klf9 biases RGL quiescence-activation decisions. Clonal lineage tracing and longitudinal intravital two-photon imaging of RGLs following cell-autonomous Klf9 deletion directly demonstrated increased symmetric self-renewal. In vivo translational profiling of RGLs identified a Klf9-dependent blueprint for genetic and metabolic programs instructing RGL quiescence and expansion. Thus, experience dependent regulation of Klf9 in RGLs may ensure self-preservation of neural stem cells while anticipating future demands for neurogenesis and astrogenesis to support hippocampal functions.
2022-01-06 | GSE164889 | GEO
Project description:Adult hippocampal neurogenesis is important for certain forms of cognition and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. However, how this balance is regulated remains poorly understood. Here we show that the rate of fatty acid oxidation (FAO) defines quiescence vs. proliferation in NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs. Pharmacological inhibition and conditional deletion of Cpt1a in vitro and in vivo leads to altered NSPC behavior, showing that Cpt1a-dependent FAO is required for stem cell maintenance and proper neurogenesis. Strikingly, experimental manipulation of malonyl-CoA, the metabolite that regulates levels of FAO, is sufficient to induce exit from quiescence and to enhance NSPC proliferation. Thus, the data presented here identify a shift in FAO metabolism that governs NSPC behavior and suggest an instructive role for fatty acid metabolism in regulating NSPC activity.
2019-11-15 | PXD005598 | Pride
Project description:Adult neural stem cells are largely quiescent, and require transcriptional reprogramming to re-enter the cell cycle before neurogenesis. However, mechanisms underlying the transcriptional overhaul during NSC activation remain undefined. Here, we identify the chromatin accessibility differences between primary neural stem/progenitor cells in quiescent and activated states. These distinct cellular states exhibit shared and unique chromatin profiles, both associated with gene regulation. Interestingly, accessible chromatin states specific to activation or quiescence are active enhancers bound by pro-neurogenic and quiescence factors, ASCL1 and NFI. In contrast, shared sites are enriched for core promoter elements associated with translation and metabolism. Unexpectedly, through integrated analysis, we find that many sites that become accessible during NSC activation are linked to downregulation of gene expression and associated with pro-quiescence factors, revealing a novel mechanism that may preserve quiescence re-entry. Together, our findings reveal how accessible chromatin states regulate the transcriptional switch between NSC quiescence and activation.
2021-11-17 | GSE161578 | GEO
Project description:Important hallmark of neurogenesis is activation of quiescent neural stem cells (NSC) in dentate gyrus. Precise mechanisms of NSC activation are not fully clear. In the current study we interrogate the role of homeodomain finger protein 2 (Phf2) in this process. Here we performed mouse transcriptome RNA-seq profiling of epigenetic regulator Phf2 in neural stem cells without and with knock-down in order to uncover mechanistic components/pathways affecting protein translational capacity in activated NSC.
2023-05-30 | GSE159311 | GEO
Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
2018-11-28 | PXD011537 | Pride
Project description:The study of the compond PIP-RBPJ-1‘ function on neural stem cell. Synthetic DNA-binding inhibitors capable of gaining precise control over neurogenesis factors could obviate the current clinical barriers associated with small molecule use in regenerative medicine. Here, we show the design and bio-efficacy of a synthetic ligand PIP-RBPJ-1 to cause promoter-specific suppression of neurogenesis-associated HES1, and its downstream genes. Furthermore, PIP-RBPJ-1 alone could alter the neural system-associated notch signaling factors and remarkably induce neurogenesis with an efficiency that is comparable to a conventional approach. Here is one day treatment of the PIP-RBPJ-1 on neural stem cells.
2018-07-19 | GSE109916 | GEO
Project description:Adult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb (OB) interneurons. Here we show that multiple regionally-distinct NSCs, including domains that are usually quiescent, are recruited on different gestation days during pregnancy. Synchronized activation of these adult NSC pools generates transient waves of short-lived OB interneurons, especially in layers with less neurogenesis under homeostasis. Using spatial transcriptomics, we identify molecular markers of pregnancy-associated interneurons, and show that some subsets are temporarily needed for own pup recognition. Thus, pregnancy triggers transient, yet behaviorally-relevant neurogenesis, highlighting the physiological relevance of adult stem cell heterogeneity.
2023-11-22 | GSE224360 | GEO