Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1058687 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:The acetylation levels of histones and other proteins change during aging and have been linked to neurodegeneration. Here we show that deletion of the histone acetyltransferase (HAT) co-factor Trrap specifically impairs the function of the transcription factor Sp1, reduces its stability and causes a decrease in histone acetylation at Sp1 target genes. Modulation of Sp1 function by Trrap acts as a hub regulating multiple processes involved in neuron and neural stem cells function and maintenance including microtubule dynamics and the Wnt signaling pathway. Consistently, Trrap conditional mutants exhibit all hallmarks of neurodegeneration including dendrite retraction and axonal swellings, neuron death, astrogliosis, microglia activation, demyelination and decreased adult neurogenesis. Our results uncovered a novel functional network, essential to prevent neurodegeneration, and involving the specific regulation of Sp1 transcription factor and its downstream targets by Trrap-HAT.
2021-02-17 | GSE131283 | GEO
Project description:Astrocyte-to-neuron conversion provides a potential strategy for neural repair, but the endogenous mechanisms that maintain astrocytic identity and restrict neuronal fate acquisition remain incompletely understood. In this study, we investigated the role of Hopx, an astrocyte-enriched transcriptional regulator, in maintaining astrocyte fate and limiting astrocyte-to-neuron conversion. We developed an AAV-compatible TIGR interference (TIGRi) system to repress Hopx expression in vivo and applied this strategy in Aldh1l1CreERT2;Rosa26-LSL-tdTomato lineage-tracing mice. To define the transcriptional changes associated with Hopx knockdown-induced astrocyte-to-neuron conversion, we performed single-cell RNA sequencing on hippocampal cells collected after AAV-TIGRi-Hopx delivery and tamoxifen induction. scRNA-seq dataset was generated to characterize the transcriptomic states of virus-transduced astrocyte-lineage cells, identify intermediate cell populations during conversion, and reconstruct the trajectory from astrocyte-like cells toward progenitor-like and neuron-like states. The analysis revealed Hopx knockdown-associated induction of neurogenic and neuronal transcriptional programs in AAV-transduced astrocyte-lineage cells, including increased expression of progenitor- and neuron-associated markers and gene modules related to generation of neurons and neuron fate commitment. These data support the conclusion that Hopx repression promotes a progressive transcriptional transition from a glial state toward a neuron-like state and provide a transcriptomic resource for studying endogenous regulation of astrocyte plasticity during in vivo neural reprogramming. In parallel, we performed HOPX ChIP-seq to define the genome-wide binding landscape of HOPX and identify HOPX peak-associated candidate genes. Together, the scRNA-seq and ChIP-seq datasets provide complementary resources for investigating the transcriptional and genomic regulatory mechanisms underlying astrocyte-to-neuron conversion in vivo.
2026-05-29 | GSE333189 | GEO
Project description:RNA-seq analysis of gene expression in cells during Ascl1 mediated astrocyte-to-neuron conversion.
| PRJNA548727 | ENA
Project description:The acetylation levels of histones and other proteins change during aging and have been linked to neurodegeneration. Here we show that deletion of the histone acetyltransferase (HAT) co-factor Trrap specifically impairs the function of the transcription factor Sp1, reduces its stability and causes a decrease in histone acetylation at Sp1 target genes. Modulation of Sp1 function by Trrap acts as a hub regulating multiple processes involved in neuron and neural stem cells function and maintenance including microtubule dynamics and the Wnt signaling pathway. Consistently, Trrap conditional mutants exhibit all hallmarks of neurodegeneration including dendrite retraction and axonal swellings, neuron death, astrogliosis, microglia activation, demyelination and decreased adult neurogenesis. Our results uncovered a novel functional network, essential to prevent neurodegeneration, and involving the specific regulation of Sp1 transcription factor and its downstream targets by Trrap-HAT.
2021-02-17 | GSE131213 | GEO
Project description:Purpose: To test the neuronal conversion and other effects induced by neural transcription factor Neurog2 or Ascl1 in human glioblastoma cells Methods: Retroviral expression of Ascl1, Neurog2 or control GFP in cultured human U251 cells at 6 DPI
2021-08-11 | GSE161534 | GEO
Project description:Here we reveal a hierarchical mechanism in the direct conversion of fibroblasts into induced neuronal (iN) cells mediated by the transcription factors Ascl1, Brn2, and Myt1l. Examination of global transcriptional changes and mapping genome-wide transcription factors occupancy at distinct time points during the transdifferentiation process
2013-04-10 | E-GEOD-43916 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Neuronal reprogramming using adeno-associated viruses (AAVs) carrying a GFAP mini-promoter to drive neurogenic transcription factor expression in astrocytes in vivo were refuted due to off-target neuronal expression. Here, we show successful neuronal conversion of pre-labeled astrocytes using AAV-GFAP to express phospho-deficient Ascl1SA6, and demonstrate that miR124 target sites reduce off-target neuronal expression. Finally, single cell transcriptomic and pseudotime trajectory analyses confirmed Ascl1SA6-driven astrocyte-to-neuron conversion, and more limited oligodendrocyte conversion events
2025-11-09 | GSE288733 | GEO
Project description:Specific neuronal types derived from embryonic stem cells (ESCs) can facilitate mechanistic studies and potentially aid in regenerative medicine. Existing induction methods, however, mostly rely on the effects of growth factors, which generally tend to result in mixed populations of neurons. Here we report that over-expression of specific transcription factors (TFs) in ESCs can rather guide the differentiation of ESCs towards specific neuron types. Analysis of published data on gene expression changes early (two days) after induction of each of 185 induced TFs implicated candidate TFs for further ESC differentiation studies. After induction for 6 days four of them (Ascl1, Smad7, Nr2f1, and Ascl2) generated a high proportion (>35%) of cells with neural progenitor marker PSA-NCAM and clear neural morphology on day 14. The capacity of these TFs to induce neural differentiation is inferred to be most likely linked to early activation of the Notch signaling pathway. Among the neuron-like cells, GABA-positive cells were most abundant (32-97% for 4 top TFs), whereas Isl1-positive cells and TH-positive cells were less abundant (<12% and <5%, respectively). Enrichment of cells obtained with the induction of Ascl1, Smad7, and Nr2f1 using beads with anti-PSA-NCAM antibody resulted in essentially pure population of neuron-like cells with expression profiles similar to neural tissues and highly expressed markers of GABAergic neurons. A time-course experiment with induction of Ascl1 showed early upregulation of most neural-specific and GABAergic-specific mRNA and miRNAs. We identified mRNA and miRNAs, whose expression depended on the induction of Ascl1, and showed that they were enriched in Ascl1 target genes. In summary, this study indicates that induction of transcription factors is a promising approach to generate candidate specific neural cell types from ESCs. Transcription factor Ascl1 was induced in mouse ESCs to facilitate neural differentiation. Expression of transgenic Ascl1 was repressed by doxycycline (Dox); thus, it were induced in Dox- conditions, whereas Dox+ conditions represent control cells with no expression of Ascl1 transgene. For neural differentiation, cells were cultured 3 days in alpha-MEM medium and then - in NeuroCult neural differentiation medium for 2-11 days (total up to 14 days). RNA was extracted with mirVana kit (Thermo Fisher Scientific).
2016-07-21 | E-GEOD-78950 | biostudies-arrayexpress