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Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs

ABSTRACT: Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs

PROVIDER: PRJNA1191437 | ENA |

REPOSITORIES: ENA

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Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs IV

Project description:Neurogenic microRNAs 9/9* and 124 (miR-9/9*-124) drive the direct reprogramming of human fibroblasts into neurons with the initiation of the fate erasure of fibroblasts. However, whether the miR-9/9*-124 fate erasure logic extends to neuronal conversion of other somatic cell types remains unknown. Here, we uncover that miR-9/9*-124 induce neuronal conversion of multiple cell types: dura fibroblasts, astrocytes, smooth muscle cells, and pericytes. We reveal the cell type-specific and pan-somatic gene network erasure induced by miR-9/9*-124, including cell cycle, morphology, and proteostasis gene networks. Leveraging these pan-somatic gene networks, we predict upstream regulators that may antagonize somatic fate erasure. Among the predicted regulators, we identify TP53 (p53) whose inhibition is sufficient to enhance neuronal conversion even in post-mitotic cells. This study extends miR-9/9*-124 reprogramming to alternate somatic cells, reveals the pan-somatic gene network fate erasure logic of miR-9/9*-124, and shows a neurogenic role for p53-inhibition in the miR-9/9*-124-signaling cascade.

2024-12-31 | GSE283009 | GEO

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs III

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Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs II

2024-12-31 | GSE283006 | GEO

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs I

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Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs II

Project description:Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs II

| PRJNA1191441 | ENA

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs III

Project description:Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs III

| PRJNA1191442 | ENA

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs I

Project description:Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs I

| PRJNA1191440 | ENA

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs IV

Project description:Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs IV

| PRJNA1191443 | ENA

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs

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

2024-12-31 | GSE283010 | GEO

Senescence impairs direct conversion of human somatic cells to neurons

Project description:Direct conversion from fibroblasts to neurons is a potential cell replacement therapy for neurological disorders, and a variety of combinations of transcription factors have been tried. We notice that the efficiency of conversion from aging fibroblasts was much lower than in early stage cells, which is consistent with the notion that cellular senescence impairs conversion of fibroblasts to neurons. Here, we found that the transient knockdown of the p16Ink4a/p19Arf locus was sufficient to convert human fibroblasts to neurons. Futhermore, expression of hTERT alone, another mechanism behind immortalization, also induced neuron conversion. Our results show that the acquisition of immortality is a crucial step for the conversion of human fibroblasts into induced neurons.

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