The DNA modification is dynamic during the conversion from fibroblasts to neurons
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE88869 | GEO | 2016/10/21
SECONDARY ACCESSION(S): PRJNA348841
REPOSITORIES: GEO
Similar Datasets
Project description:Expression level of 5mC during the conversion from fibroblasts to neurons
2016-10-21 | GSE88868 | GEO
Project description:Expression level of 5mC during the conversion from fibroblasts to neurons
2016-10-21 | GSE88867 | GEO
Project description:The DNA modification is dynamic during the conversion from fibroblasts to neurons
| PRJNA348841 | ENA
Project description:Humans and mice detect pain, itch, temperature, pressure, stretch and limb position via signaling from peripheral sensory neurons. These neurons are divided into three functional classes (nociceptors/pruritoceptors, mechanoreceptors and proprioceptors) that are distinguished by their selective expression of TrkA, TrkB or TrkC receptors, respectively. We found that transiently coexpressing Brn3a with either Ngn1 or Ngn2 selectively reprogrammed human and mouse fibroblasts to acquire key properties of these three classes of sensory neurons. These induced sensory neurons (iSNs) were electrically active, exhibited distinct sensory neuron morphologies and matched the characteristic gene expression patterns of endogenous sensory neurons, including selective expression of Trk receptors. In addition, we found that calcium-imaging assays could identify subsets of iSNs that selectively responded to diverse ligands known to activate itch- and pain-sensing neurons. These results offer a simple and rapid means for producing genetically diverse human sensory neurons suitable for drug screening and mechanistic studies.
| S-EPMC4466122 | biostudies-literature
Project description:Neurogenic transcription factors and evolutionarily conserved signalling pathways have been found to be instrumental in the formation of neurons. However, the instructive role of microRNAs (miRNAs) in neurogenesis remains unexplored. We recently discovered that miR-9* and miR-124 instruct compositional changes of SWI/SNF-like BAF chromatin-remodelling complexes, a process important for neuronal differentiation and function. Nearing mitotic exit of neural progenitors, miR-9* and miR-124 repress the BAF53a subunit of the neural-progenitor (np)BAF chromatin-remodelling complex. After mitotic exit, BAF53a is replaced by BAF53b, and BAF45a by BAF45b and BAF45c, which are then incorporated into neuron-specific (n)BAF complexes essential for post-mitotic functions. Because miR-9/9* and miR-124 also control multiple genes regulating neuronal differentiation and function, we proposed that these miRNAs might contribute to neuronal fates. Here we show that expression of miR-9/9* and miR-124 (miR-9/9*-124) in human fibroblasts induces their conversion into neurons, a process facilitated by NEUROD2. Further addition of neurogenic transcription factors ASCL1 and MYT1L enhances the rate of conversion and the maturation of the converted neurons, whereas expression of these transcription factors alone without miR-9/9*-124 was ineffective. These studies indicate that the genetic circuitry involving miR-9/9*-124 can have an instructive role in neural fate determination.
| S-EPMC3348862 | biostudies-literature
Project description:Summary Generation of patient-derived neurons provides an unprecedented approach in modeling neurological diseases. Here, we describe the direct conversion of adult fibroblasts into motor neurons via lentiviral delivery of transcription factors. Compared with iPSC-based approach, directly converted neurons from donors retain features associated with age, making them ideal systems for modeling age-related neurological diseases. Low yield is the major challenge of this protocol. High quality lentiviruses and optimized cell culture conditions are critical to improve the final yield. For complete details on the use and execution of this protocol, please refer to Ding et al. (2020), Ding et al. (2021), and Liu et al. (2016) Graphical abstract Highlights • Detailed protocol to generate MNs from human adult fibroblasts• Protocol assesses the identity and efficiency of MN generation in vitro• Descriptions of troubleshooting common problems during the reprogramming process Generation of patient-derived neurons provides an unprecedented approach in modeling neurological diseases. Here, we describe the direct conversion of adult fibroblasts into motor neurons via lentiviral delivery of transcription factors. Compared with iPSC-based approach, directly converted neurons from donors retain features associated with age, making them ideal systems for modeling age-related neurological diseases. Low yield is the major challenge of this protocol. High quality lentiviruses and optimized cell culture conditions are critical to improve the final yield.
| S-EPMC8554625 | biostudies-literature
Project description:Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combined expression of defined factors. Here we show that the same strategy can be applied to human embryonic and postnatal fibroblasts. By overexpression of the transcription factors Ascl1, Brn2, and Myt1l, human fibroblasts were efficiently converted to functional neurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided together with the three conversion factors. By combining expression of the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2, we could direct the phenotype of the converted cells toward dopaminergic neurons. Such subtype-specific induced neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy.
| S-EPMC3121829 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-09-18 | GSE40927 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-08-31 | GSE94712 | GEO
Project description:Serotonergic (5HT) neurons exert diverse and widespread functions in the brain. Dysfunction of the serotonergic system gives rise to a variety of mental illnesses including depression, anxiety, obsessive compulsive disorder, autism and eating disorders. Here we show that human primary fibroblasts were directly converted to induced serotonergic (i5HT) neurons by the expression of Ascl1, Foxa2, Lmx1b and FEV. The transdifferentiation was enhanced by p53 knockdown and appropriate culture conditions including hypoxia. The i5HT neurons expressed markers for mature serotonergic neurons, had Ca(2+)-dependent 5HT release and selective 5HT uptake, exhibited spontaneous action potentials and spontaneous excitatory postsynaptic currents. Application of serotonin significantly increased the firing rate of spontaneous action potentials, demonstrating the functional utility of i5HT neurons for studying serotonergic neurotransmission. The availability of human i5HT neurons will be very useful for research and drug discovery on many serotonin-related mental disorders.
| S-EPMC4518549 | biostudies-literature