Revisiting NeuroD1-mediated Glia-to-Neuron Trans-differentiation Using Transgenic Mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE290098 | GEO | 2025/06/18
REPOSITORIES: GEO
Similar Datasets
Project description:NeuroD1-mediated in situ astrocyte-to-neuron conversion can regenerate a large number of functional new neurons after ischemic injury. RNA-sequencing was conducted to confirm neuronal recovery after cell conversion at the mRNA level.
2019-08-20 | GSE135981 | GEO
Project description:Spinal cord injury (SCI) is a common but devastating trauma of the central nerve system. In this study, we reprogrammed cultured spinal-cord reactive astrocytes into neurons by Neurod1 expression. The mechanism of programmed conversion from astrocytes to neurons has not been clarified yet. Thus, we used label-free proteomics to identify differentially expressed proteins in Neurod1 over-expressed astrocytes and control group. A total of 1952 proteins were identified, including 92 significantly changed proteins. Among these proteins, 8 proteins were identified as candidates involving in the process of the reprogramming, based on their biological function and fold change in the bioinformatic analysis. Our study revealed that that Neurod1 can directly reprogram cultured spinal-cord reactive astrocytes into neurons, and several proteins that could play a significant role during the neuronal reprogramming were discovered.
2021-09-08 | PXD016097 | Pride
Project description:Astrocyte-to-neuron conversion has developed into a promising avenue for neuronal replacement therapy. Neurons depend critically on mitochondria function and often die by ferroptosis during the conversion process. Here we examined the extent of adequate mitochondrial reprogramming by morphology and proteome analysis. While mitochondria profoundly changed their morphology during Neurogenin2 (Neurog2) – or Achaete-scute homolog 1 (Ascl1)-mediated astrocyte-to-neuron reprogramming, we found neuron-specific mitochondrial proteins, here identified in a comprehensive proteome analysis of isolated mitochondria from primary neurons and astrocytes, to be only partially and at late stages regulated during the process. To improve this, we used dCas9 technology to induce neuron-specific mitochondrial proteins early during reprogramming. This resulted not only in increased conversion efficiency, but also in faster neuronal generation. Taken together, reprogramming mitochondria in a cell type-specific manner has powerful effects on astrocyte-to-neuron conversion, suggesting mitochondria to be a driving force in this process.
2021-03-29 | PXD014886 | Pride
Project description:Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led to dysregulated α−motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α−but not of adjacent γ−motor neurons. Additionally, a subset of TrkA+ sensory afferents projected to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement. 12 total samples consisting of three biological replicates each of flow sorted postnatal day 7 dorsal spinal cord astrocytes, ventral spinal cord astrocytes, dorsal SC non astrocytes, and ventral SC non astrocytes
2014-05-02 | E-GEOD-55054 | biostudies-arrayexpress
Project description:Aubert2005 - Interaction between astrocytes
and neurons on energy metabolism
Enocded non-curated model. Issues:
- Confusing equations A.41 and A.42
- Missing values for parameters Vv,0 and dHb,0
This model is described in the article:
Interaction between
astrocytes and neurons studied using a mathematical model of
compartmentalized energy metabolism.
Aubert A, Costalat R.
J. Cereb. Blood Flow Metab. 2005 Nov;
25(11): 1476-1490
Abstract:
Understanding cerebral energy metabolism in neurons and
astrocytes is necessary for the interpretation of functional
brain imaging data. It has been suggested that astrocytes can
provide lactate as an energy fuel to neurons, a process
referred to as astrocyte-neuron lactate shuttle (ANLS). Some
authors challenged this hypothesis, defending the classical
view that glucose is the major energy substrate of neurons, at
rest as well as in response to a stimulation. To test the ANLS
hypothesis from a theoretical point of view, we developed a
mathematical model of compartmentalized energy metabolism
between neurons and astrocytes, adopting hypotheses highly
unfavorable to ANLS. Simulation results can be divided between
two groups, depending on the relative neuron versus astrocyte
stimulation. If this ratio is low, ANLS is observed during all
the stimulus and poststimulus periods (continuous ANLS), but a
high ratio induces ANLS only at the beginning of the stimulus
and during the poststimulus period (triphasic behavior).
Finally, our results show that current experimental data on
lactate kinetics are compatible with the ANLS hypothesis, and
that it is essential to assess the neuronal and astrocytic
NADH/NAD+ ratio changes to test the ANLS hypothesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1411210000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-02-25 | MODEL1411210000 | BioModels
Project description:Profiling of transcriptional changes in rat astrocytes when co-cultured with neurons: comparison of astrocytes cultured alone with astrocytes co-cultured with mouse hippocampal neurons. Co-cultured astrocytes are isolated using cold jet, a novel tool for these neuron-glia cultures. Over the last decade, the importance of astrocyte-neuron communication in neuronal development and synaptic plasticity has become increasingly clear. Since neuron-astrocyte interactions represent highly dynamic and reciprocal processes, we hypothesized that at least part of the involved astrocyte genes may be regulated as a consequence of their interactions with maturing neurons. In order to identify such neuron-induced astrocyte genes in vitro, we tested the effectiveness of the ‘cold jet’, a new method for separation of neurons from co-cultured astrocytes. The cold jet method is performed under ice-cold conditions and avoids protease-mediated isolation of astrocytes or time-consuming centrifugation, yielding intact astrocyte mRNA with approximately 90% of neuronal RNA removed. Using this method, we executed genome-wide profiling in which RNA derived from astrocyte-only cultures was compared with astrocyte RNA derived from differentiating neuron-astrocyte co-cultures. Data analysis revealed changes in expression of a large number of mRNAs and biological processes, including novel findings. Thus, cold jet is an efficient method to separate astrocytes from neurons in co-culture, and in this study reveals that neurons induce robust gene-expression changes in co-cultured astrocytes.
2016-11-09 | GSE52481 | GEO
Project description:Astrocytes and neurons coexist and interact in the CNS1,2. Given that many signaling and pathological events are protein-driven, identifying astrocyte and neuron proteomes is essential for elucidating the complex protein networks that dictate their respective contributions to physiology and disease. Here, we used cell- and subcompartment-specific proximity-dependent biotinylation3 to study the proteomes of striatal astrocytes and medium spiny neurons (MSNs) in vivo. We evaluated cytosolic and plasma membrane compartments for astrocytes and MSNs, revealing how these cells differ at the protein level and in their core signaling machinery. We assessed subcellular compartments of astrocytes including end feet and processes to reveal the molecular basis of essential astrocyte signaling and homeostatic functions. Unexpectedly, SAPAP3 proteins (gene; Dlgap3) associated with obsessive compulsive disorder (OCD) and repetitive behaviors4-11 were detected at equivalent levels in striatal astrocyte and MSN plasma membrane and cytosolic compartments. Astrocytic expression was confirmed by RNA-seq, fluorescence in situ hybridization and immunohistochemistry. Furthermore, genetic rescue experiments combined with behavioral analyses and proteomics in a mouse model4 of OCD lacking SAPAP3 revealed contributions of SAPAP3 in astrocytes and MSNs to repetitive and anxiety-related OCD behaviors. Our data define how astrocytes and neurons differ at the protein level and in their major signaling pathways, how astrocyte proteomes vary between physiological subcompartments, and how specific astrocyte and neuronal molecular mechanisms contribute to a psychiatric disease. Targeting both astrocytes and neurons together is likely to be therapeutically effective in complex CNS disorders.
2023-01-13 | PXD029257 | Pride
Project description:Neurons induce a dramatic transformation in developing astrocytes, causing them to develop a complex stellate morphology resembling their appearance in vivo. However, the transcriptional changes that accompany this transformation are not known, nor are the signalling mechanisms responsible. Similarly, whether synaptic activity controls astrocytic gene expression and whether this leads to altered astrocytic function is unclear. This experiment seeks to investigate this non-cell-autonomously regulated gene expression by co-culturing astrocytes and neurons derived from closely related species (mouse and rat), and separating RNA-seq reads derived from each cell type in silico, thus shedding light on the signalling mechanisms underlying neuron-to-astrocyte communication and the functional consequences for astrocytes.
2017-05-02 | E-MTAB-5514 | biostudies-arrayexpress
Project description:Astrocytes are essential cells of the central nervous system, characterized by dynamic relationships with neurons that range from functional metabolic interactions and regulation of neuronal firing activities, to the release of neurotrophic and neuroprotective factors. In Parkinson’s disease (PD), dopaminergic neurons are a vulnerable population progressively lost during the course of the disease, but the effects of PD on astrocytes and astrocyte-to-neuron communication remains mostly unknown. This study focuses on the effects of the PD-related mutation LRRK2 G2019S in astrocytes, using patient-derived induced pluripotent stem cells. We report the alteration of extracellular vesicle (EV) biogenesis in astrocytes, and we identify the abnormal accumulation of key PD-related proteins within multi vesicular bodies (MVBs). We found that dopaminergic neurons internalize astrocyte-secreted EVs but LRRK2 G2019S EVs are abnormally enriched in the neurites and provide only marginal neurotrophic support to dopaminergic neurons. Thus, dysfunctional astrocyte-to-neuron communication via altered EV biological properties could participate in the progression of PD.
2021-10-06 | GSE152768 | GEO
Project description:Astrocytes are essential regulators of the central nervous systems response to disease and injury and have been hypothesized to actively kill neurons in neurodegenerative disease. There has been intense interest in identifying the putative toxic factor(s) secreted by astrocytes. Here, we report a biochemical approach to isolate the astrocyte-derived toxic factor. Unexpectedly, instead of a protein, we found saturated lipids contained in ApoE/ApoJ lipoparticles as components of astrocyte-mediated toxicity in vitro and in vivo. Eliminating the formation of long-chain saturated lipids by astrocyte cell-type-specific knockout of the saturated lipid synthesis enzyme ELOVL1 mitigates astrocyte-mediated toxicity in vitro as well as in an acute axonal injury model in vivo. These results suggest a new mechanism by which astrocytes kill cells in the CNS.
2021-07-12 | MSV000087805 | MassIVE