Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA227463 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:2D Direct conversion of human dopaminergic neurons
| PRJNA1204375 | ENA
Project description:Direct conversion from fibroblast to neuron has recently been successfully induced bypassing the pluripotent state. However, the conversion takes a few months with low percentages of success. Here we found that depletion of p53, which can converted fibroblasts into three major neural lineages: neurons, astrocytes and oligodendrocytes. Furthermore, our method provided a high efficiency of conversion in aging fibroblasts, where published methods failed. This finding may help developing a prototype for neuron replacement therapy, including foraging people vulnerable to neurological disorders. p53 has been shown to inhibit reprogramming of fibroblasts to iPS cells, by depletion of p53 in human fibroblasts, we study the function of p53 in induced neuron process. By induction of p53 knockdown fibroblasts with special neuron medium, we can get mature neurons directly. In the induction process, many neurogenic transcription factors were up-regulated, and we prove that p21 is not involved in this process.
2013-04-26 | E-GEOD-46392 | biostudies-arrayexpress
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. Transient knockdown of p16/p19 or p53 expression or exogenous overexpression of hTERT can induce primary fibroblasts to immortality. In the following, treated cells were cultured in neuron-induction medium. We can observe the morphology change and detect the neuronal markers. Also, some of the induced neurons could generate action potentials and neurotransmitter-induced currents in optimal conditions.
2012-12-28 | E-GEOD-43175 | biostudies-arrayexpress
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 | GSE283006 | GEO
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 | GSE283004 | GEO
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
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 | GSE283008 | GEO
Project description:We have generated isogenic induced pluripotent stem cell lines by reprogramming human fibroblasts from patients carrying the LRRK2 G2019S mutation with subsequent zinc finger nuclease - mediated targeted correction of the diseased allele. These iPS cell lines were differentiated for 30 days using a direct differentiation protocol towards midbrain dopaminergic neurons (mDANs). Isogenic human iPS cells carrying the LRRK2 WT and G2019S locus were differentiated to dopaminergic neurons to detect gene expression changes associated with mutated LRRK2.
2013-03-07 | E-GEOD-43364 | biostudies-arrayexpress
Project description:Direct conversion of fibroblasts to neurons by a new mechanism – p53 regulation
| PRJNA199749 | ENA
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.
2012-12-28 | GSE43175 | GEO