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Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes

ABSTRACT: Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes

PROVIDER: PRJNA1041804 | ENA |

REPOSITORIES: ENA

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Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [Bulk RNA-seq]

Project description:Mitochondria account for essential cellular pathways, from ATP production to nucleotide metabolism, and their deficits lead to neurological disorders and contribute to the onset of age-related diseases. Direct neuronal reprogramming aims at replacing neurons lost in such conditions, but almost nothing is known about the impact of mitochondrial dysfunction in human cell direct reprogramming. Here we explore the defects and how to improve the neuronal reprogramming of iPSC-derived astrocytes carrying mutations in NDUFS4 gene, important for Complex I and associated to Leigh Sydrome. This led to the identification of the unfolded protein response as a major hurdle in the direct neuronal conversion of not only patient, but also control astrocytes and fibroblasts. Our data highlight mitochondria-ER stress-mediated inhibition of translation as a key hurdle in direct neuronal reprogramming, emphasizing how disease modelling using patient cells can contribute to unravel novel pathways in human glia cell reprogramming.

2024-01-24 | GSE248120 | GEO

Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [scRNA-seq 5 day]

2024-01-24 | GSE248122 | GEO

Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [scRNA-seq day 20]

2024-01-24 | GSE248128 | GEO

Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [Bulk RNA-seq]

Project description:Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [Bulk RNA-seq]

| PRJNA1041800 | ENA

Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [scRNA-seq 5 day]

Project description:Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [scRNA-seq 5 day]

| PRJNA1041802 | ENA

Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [scRNA-seq day 20]

Project description:Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [scRNA-seq day 20]

| PRJNA1041808 | ENA

Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-01-24 | GSE248129 | GEO

DIRECT CONVERSION OF FIBROBLASTS INTO FUNCTIONAL ASTROCYTES BY DEFINED TRANSCRIPTION FACTORS

Project description:Direct cell reprogramming has enabled the direct conversion of skin fibroblasts into functional neurons and oligodendrocytes using a minimal set of cell lineage-specific transcription factors. This approach has substantial advantages since it is rapid and simple, generating the cell type of interest in a single step. However, it remains unknown whether this technology can be applied for directly reprogramming skin cells into astrocytes, the third neural lineage. Astrocytes play crucial roles in neuronal homeostasis and their dysfunctions contribute to the origin and progression of multiple human diseases. Herein, we carried out a screening using several transcription factors involved in defining the astroglial cell fate and identified NFIA, NFIB and SOX9 to be sufficient to convert with high efficiency embryonic and post-natal mouse fibroblasts into astrocytes (iAstrocytes). We proved both by gene expression profiling and functional tests that iAstrocytes are comparable to native brain astrocytes. This protocol can be then employed to generate functional iAstrocytes for a wide range of experimental applications. Induced astrocytes (iAstro) were compared to Fibroblasts (Fibro) as negative control and to primary astrocytes (astro) as positive control. Three biological replicates were analyzed for each experimental group.

2015-06-22 | E-GEOD-59018 | biostudies-arrayexpress

Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules

Project description:Astrocytes, due to the proximity to neuronal lineage and capability to proliferate, are ideal starting cells to regenerate neurons. Human fetal astrocytes have been successfully converted into neuronal cells by small molecules, which offer a broader range of further applications than transcription factor-mediated neuronal reprogramming. Here we report human adult astrocytes could also be converted into neuronal cells by a different set with fewer small molecules. These induced neuronal cells exhibited typical neuronal morphologies, expressed neuronal markers, and displayed neuronal electrophysiological properties. Genome-wide RNA-sequencing analysis showed the gene expression profile of induced neuronal cells resembled that of human embryonic stem cell-differentiated neurons. When transplanted into postnatal mouse brains, these induced neuronal cells could survive in vivo. Altogether, our study provides a new strategy to directly generate transgene-free neurons from human adult astrocytes by small molecules.

2017-06-12 | GSE84826 | GEO

DIRECT CONVERSION OF FIBROBLASTS INTO FUNCTIONAL ASTROCYTES BY DEFINED TRANSCRIPTION FACTORS

2015-06-22 | GSE59018 | GEO