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A NeuroD1 AAV-Based Gene Therapy For Functional Brain Repair After Ischemic Injury Through In Vivo Astrocyte-To-Neuron Conversion

ABSTRACT: A NeuroD1 AAV-Based Gene Therapy For Functional Brain Repair After Ischemic Injury Through In Vivo Astrocyte-To-Neuron Conversion

PROVIDER: PRJNA560878 | ENA |

REPOSITORIES: ENA

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A NeuroD1 AAV-Based Gene Therapy For Functional Brain Repair After Ischemic Injury Through In Vivo Astrocyte-To-Neuron Conversion

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

Transcriptional changes and microRNA expression profiles during NeuroD1-mediated astrocyte-to-neuron conversion

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A NeuroD1 AAV-Based Gene Therapy for Functional Brain Repair after Ischemic Injury through In Vivo Astrocyte-to-Neuron Conversion.

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Neuron-Derived Estrogen is Critical for Astrocyte Activation and Neuroprotection of the Ischemic Brain

Project description:We examined the transcriptional changes modulated in ischemic brain of fore brain specific aromatase knockout mice (FBN-ARO-KO) by performing global transcriptome analysis.Total RNA was isolated from FLOX and FBN-ARO-KO mice that underwent 20-minute CCA occlusion, followed by 24-hour reperfusion. The collected hippocampi samples were subjected to RNA isolation and Illumina TruSeq RNA sample preparation and sequencing was done using UT Health San Antonio genomics core facility protocol. We observed that some of the key pathways that regulate astrocyte reactivity, such as RhoA signaling, actin-based motility by Rho signaling, signaling by Rho family GTPases, and protein ubiquitination, NRF2-mediated oxidative stress response pathways were significantly altered in FBN-ARO-KO+GCI mice.

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Neuron-Derived Estrogen is Critical for Astrocyte Activation and Neuroprotection of the Ischemic Brain

Project description:Neuron-Derived Estrogen is Critical for Astrocyte Activation and Neuroprotection of the Ischemic Brain

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RNA-seq analysis of gene expression in cells during Ascl1 mediated astrocyte-to-neuron conversion.

Project description:We analyzed the transcriptomic changes in cells sorted from astrocyte-to-neuron conversion at different stages, identified the differentially expressed genes (DEGs), and functionally validated the critical DEGs.

2020-12-29 | GSE132674 | GEO

Astrocyte-Derived Estrogen Regulates Reactive Astrogliosis and is Neuroprotective Following Ischemic Brain Injury

Project description:We examined the transcriptional changes modulated in ischemic brain of astrocyte specific aromatase knockout mice (GFAP-ARO-KO) by performing global transcriptome analysis.Total RNA was isolated from FLOX and GFAP-ARO-KO mice that underwent 20-minute CCA occlusion, followed by 24-hour reperfusion. The collected hippocampi samples were subjected to RNA isolation and Illumina TruSeq RNA sample preparation and sequencing was done using UT Health San Antonio genomics core facility protocol. We observed that that the ischemic GFAP-ARO-KO mouse hippocampus failed to upregulate a group of genes, which have been suggested to represent the “A2” neuroprotective signature of astrocytes. In addition, the JAK-STAT3 pathway, which is critical for the induction of reactive astrogliosis, was significantly down-regulated in the GFAP-ARO-KO hippocampus following GCI. Additional pathways that altered in GFAP-ARO-KO hippocampus were related to cytokine, chemokine and inflammatory signaling pathways.

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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

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