Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA182938 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR628446.fastq.gz | Fastqsanger.gz | |||
| SRR628447.fastq.gz | Fastqsanger.gz | |||
| SRR628448.fastq.gz | Fastqsanger.gz | |||
| SRR628449.fastq.gz | Fastqsanger.gz | |||
| SRR628450.fastq.gz | Fastqsanger.gz |
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Project description:Direct conversion of somatic cells into neurons holds great promise for regenerative medicine. However, neuronal conversion is relatively inefficient in human cells compared to mouse cells. It has been unclear what might be the key barriers to reprogramming in human cells. We recently elucidated an RNA program mediated by the polypyrimidine tract binding protein PTB to convert mouse embryonic fibroblasts (MEFs) into functional neurons. In human adult fibroblasts (HAFs), however, we unexpectedly found that invoking the documented PTB–REST–miR-124 loop generates only immature neurons. We now report that the functionality requires sequential inactivation of PTB and the PTB paralog nPTB in HAFs. Inactivation of nPTB triggers another self-enforcing loop essential for neuronal maturation, which comprises nPTB, the transcription factor BRN2, and miR-9. These findings suggest that two separate gatekeepers control neuronal conversion and maturation and consecutively overcoming these gatekeepers enables deterministic reprogramming of HAFs into functional neurons.
2016-04-25 | GSE77523 | GEO
Project description:Direct conversion of somatic cells into neurons holds great promise for regenerative medicine. However, neuronal conversion is relatively inefficient in human cells compared to mouse cells. It has been unclear what might be the key barriers to reprogramming in human cells. We recently elucidated an RNA program mediated by the polypyrimidine tract binding protein PTB to convert mouse embryonic fibroblasts (MEFs) into functional neurons. In human adult fibroblasts (HAFs), however, we unexpectedly found that invoking the documented PTB–REST–miR-124 loop generates only immature neurons. We now report that the functionality requires sequential inactivation of PTB and the PTB paralog nPTB in HAFs. Inactivation of nPTB triggers another self-enforcing loop essential for neuronal maturation, which comprises nPTB, the transcription factor BRN2, and miR-9. These findings suggest that two separate gatekeepers control neuronal conversion and maturation and consecutively overcoming these gatekeepers enables deterministic reprogramming of HAFs into functional neurons.
2016-04-25 | GSE74814 | GEO
Project description:The induction of pluripotency or trans-differentiation of one cell type to another can be accomplished with cell lineage-specific transcription factors. Here we report that repression of a single RNA binding protein PTB, which occurs during normal brain development via the action of miR-124, is sufficient to induce trans-differentiation of fibroblasts into functional neurons. Besides its traditional role in regulated splicing, we show that PTB has a previously undocumented function in the regulation of microRNA functions, suppressing or enhancing microRNA targeting by competitive binding on target mRNA or altering local RNA secondary structure. A key event during neuronal induction is the relief of PTB-mediated blockage of microRNA action on multiple components of the REST complex, thereby de-repressing a large array of neuronal genes, including miR-124 and multiple neuronal-specific transcription factors, in non-neuronal cells. This converts a negative feedback loop to a positive one to elicit cellular reprogramming to the neuronal lineage. Examination of PTB regulated AGO2/microRNA targeting in Hela cells by CLIP-seq (two biological replicates) , paired-end RNA-seq (control and PTB knockdown) and 3’end stability RNA-seq (control and PTB knockdown)
2013-01-17 | E-GEOD-42701 | biostudies-arrayexpress
Project description:The induction of pluripotency or trans-differentiation of one cell type to another can be accomplished with cell lineage-specific transcription factors. Here we report that repression of a single RNA binding protein PTB, which occurs during normal brain development via the action of miR-124, is sufficient to induce trans-differentiation of fibroblasts into functional neurons. Besides its traditional role in regulated splicing, we show that PTB has a previously undocumented function in the regulation of microRNA functions, suppressing or enhancing microRNA targeting by competitive binding on target mRNA or altering local RNA secondary structure. A key event during neuronal induction is the relief of PTB-mediated blockage of microRNA action on multiple components of the REST complex, thereby de-repressing a large array of neuronal genes, including miR-124 and multiple neuronal-specific transcription factors, in non-neuronal cells. This converts a negative feedback loop to a positive one to elicit cellular reprogramming to the neuronal lineage.
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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:Neuronal microRNAs, miR-9/9* and miR-124 (miR-9/9*-124), exert reprogramming activities to direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and enable the generation of discrete neuronal subtypes with additional transcription factors. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone and reveal the surprising capability of miR-9/9*-124 in coordinately stimulating the reconfiguration of chromatin accessibilities, DNA methylation and transcriptome, leading to the generation of functionally excitable neurons, yet unbiased towards a particular subtype-lineage. We show that the microRNA-induced neuronal state enables additional transcription factors, ISL1 and LHX3, to selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons.
2017-08-04 | GSE102021 | GEO
Project description:Neuronal microRNAs, miR-9/9* and miR-124 (miR-9/9*-124), exert reprogramming activities to direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and enable the generation of discrete neuronal subtypes with additional transcription factors. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone and reveal the surprising capability of miR-9/9*-124 in coordinately stimulating the reconfiguration of chromatin accessibilities, DNA methylation and transcriptome, leading to the generation of functionally excitable neurons, yet unbiased towards a particular subtype-lineage. We show that the microRNA-induced neuronal state enables additional transcription factors, ISL1 and LHX3, to selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons.
2017-08-04 | GSE102024 | GEO
Project description:Neuronal microRNAs, miR-9/9* and miR-124 (miR-9/9*-124), exert reprogramming activities to direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and enable the generation of discrete neuronal subtypes with additional transcription factors. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone and reveal the surprising capability of miR-9/9*-124 in coordinately stimulating the reconfiguration of chromatin accessibilities, DNA methylation and transcriptome, leading to the generation of functionally excitable neurons, yet unbiased towards a particular subtype-lineage. We show that the microRNA-induced neuronal state enables additional transcription factors, ISL1 and LHX3, to selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons.
2017-08-04 | GSE102022 | GEO
Project description:Neuronal microRNAs, miR-9/9* and miR-124 (miR-9/9*-124), exert reprogramming activities to direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and enable the generation of discrete neuronal subtypes with additional transcription factors. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone and reveal the surprising capability of miR-9/9*-124 in coordinately stimulating the reconfiguration of chromatin accessibilities, DNA methylation and transcriptome, leading to the generation of functionally excitable neurons, yet unbiased towards a particular subtype-lineage. We show that the microRNA-induced neuronal state enables additional transcription factors, ISL1 and LHX3, to selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons.
2017-08-04 | GSE102033 | GEO
Project description:Neuronal microRNAs, miR-9/9* and miR-124 (miR-9/9*-124), exert reprogramming activities to direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and enable the generation of discrete neuronal subtypes with additional transcription factors. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone and reveal the surprising capability of miR-9/9*-124 in coordinately stimulating the reconfiguration of chromatin accessibilities, DNA methylation and transcriptome, leading to the generation of functionally excitable neurons, yet unbiased towards a particular subtype-lineage. We show that the microRNA-induced neuronal state enables additional transcription factors, ISL1 and LHX3, to selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons.
2017-08-04 | GSE102025 | GEO