Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cell cycle and P53 gate the direct conversion of human fibroblasts to dopaminergic neurons

ABSTRACT: Suppression of P53 in conjunction with cell cycle arrest at G1 and appropriate extracellular environment markedly increases the efficiency in the transdifferentiation of human fibroblasts to iDA neurons bt Ascl1, Nurr1, Lmx1a and miR-124.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52352 | GEO | 2015/12/02

SECONDARY ACCESSION(S): PRJNA227463

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PRRX2 and HEY2 double knock-down facilitates ASCL1-induced neuron conversion in human dermal fibroblasts.

Project description:Forced expression of ASCL1, Nurr1, Lmx1a, miRNA-124 and p53shRNA (ANLmp) in fibroblasts reprograms fibroblasts to induced dopaminergic neurons (iDA). While human lung fibroblasts can be converted rapidly and efficiently, iDA of dermal fibroblast is very unefficient and incompleted. To address this issue, we performed time series RNAseq on both lung and dermal fibroblasts during the first four days of ANLmp induced neuron convertion. Bioinformatics analysis revealed the stable fibroblast gene regulatory network (GRN) was a potential repressive factor for iDA in human dermal fibroblasts.

2019-06-17 | GSE125692 | GEO

PRRX2 and HEY2 double knock-down facilitates ASCL1-induced neuron conversion in human dermal fibroblasts II

Project description:Forced expression of ASCL1, Nurr1, Lmx1a, miRNA-124 and p53shRNA (ANLmp) in fibroblasts reprograms fibroblasts to induced dopaminergic neurons (iDA). While human lung fibroblasts can be converted rapidly and efficiently, iDA of dermal fibroblast is very unefficient and incompleted. To address this issue, we performed time series RNAseq on both lung and dermal fibroblasts during the first several days of ANLmp induced neuron convertion. Bioinformatics analysis revealed the stable fibroblast gene regulatory network (GRN) was a potential repressive factor for iDA in human dermal fibroblasts.

2019-06-17 | GSE129358 | GEO

Ascl1, Nurr1 and Lmx1 convert mouse and human fibroblasts into functional dopaminergic neurons without passing through an intermediate precursor state

Project description:Lineage-specific transcription factors, which drive cellular identity during embryogenesis, have been shown to convert cell fate when express ectopically in heterologous cells. Herein, we screened the key molecular factors governing the dopaminergic neuronal specification during brain development for their ability to generate similar neurons directly from mouse and human fibroblasts. Remarkably, we found a minimal set of three factors Mash1, Nurr1 and Lmx1a/b able to elicit such cellular reprogramming. Molecular and transcriptome studies showed reprogrammed DA neurons to faithfully recapitulate gene expression of their brain homolog cells while lacking expression of other catecholaminergic neuronal types. Induced neurons showed spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain DA neurons. The three factors were able to elicit DA neuronal conversion in human fibroblasts from prenatal or adult fibroblasts of healthy donors and a Parkinson’s disease patient. Generation of DA induced neurons from somatic cells might have significant implications in studies of neural development, disease in vitro modeling and cell replacement therapies. We infected mouse embryonic fibroblasts (MEFs) isolated from TH-GFP knock-in mice embryos at E14.5, with lentiviruses expressing the three dopaminergic transcription factors Ascl1, Lmx1a and Nurr1. TH-GFP MEFs infected (Ind) by a pool of the three previously mentioned dopaminergic lentiviruses were shifted in a neuronal medium for 12 days and sorted for GFP-positive cells. Thus we extracted mRNA from Ind-GFP-positive cells and compared them to not infetced (NI) cells by means of RNA-microarray analysis.

2011-07-04 | E-GEOD-27174 | biostudies-arrayexpress

EH004: Lmx1a encodes a rostral set of mesodiencephalic dopaminergic neurons marked by the Wnt/b-catenin signaling activator Rspo2

Project description:Recent developments in molecular programming of mesodiencephalic dopaminergic (mdDA) neurons have led to the identification of many transcription factors playing a role in mdDA specification. LIM homeodomain transcription factor Lmx1a is essential for chick mdDA development, and for the efficient differentiation of ES-cells towards a dopaminergic phenotype. In this study, we aimed towards a more detailed understanding of the subtle phenotype in Lmx1a-dr/dr mice. Therefore, microarray analysis was performed, to elucidate the exact molecular programming underlying the neuronal deficits after loss of Lmx1a. Subsequent expression analysis confirmed that Nurr1 is regulated by Lmx1a, and additional downstream targets were identified, like Pou4f1, Pbx1, Pitx2, C130021l20Rik, Calb2 and Rspo2. In line with a specific, rostral-lateral loss of expression of most of these genes during development, Nurr1 and C130021l20Rik were affected in the SNc of the mature mdDA system. Interestingly, this deficit was marked by the complete loss of the Wnt/b-catenin signaling activator Rspo2 in this domain. Expression analysis in Rspo2-/- embryos revealed affected mdDA neurons, partially phenocopying the Lmx1a mutant. Together, in this study we reveal that Lmx1a is essential for a rostral-lateral subset of the mdDA neuronal field, where it might serve a critical function in modulating proliferation and differentiation of mdDA progenitors through the activation of the Wnt activator Rspo2. Microarray expression study comparing 4 samples of homozygous LMX1A dr/dr mice, midbrain E12.5 with a pooled sample of their wt/wt littermates. Two samples were analyzed in opposite dye orientation.

2013-12-13 | E-GEOD-45831 | biostudies-arrayexpress

EH004: Lmx1a encodes a rostral set of mesodiencephalic dopaminergic neurons marked by the Wnt/b-catenin signaling activator Rspo2

2013-12-13 | GSE45831 | GEO

LCM-seq of resident NG2 glia reprogrammed to neurons in vivo using the transcription factors Ascl1, Lmx1a and Nurr1 (ALN)

Project description:Reprogramming resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward towards the possibility of treating brain injuries or diseases. Here, we show that neurons reprogrammed using Ascl1, Lmx1a and Nurr1 functionally mature and integrate into existing brain circuitry, and that the majority of the reprogrammed neurons have properties of fast spiking, parvalbumin-containing interneurons.

2017-08-29 | GSE101091 | GEO

Transcriptome analysis of human immortilized astrocytes reprogrammed into dopaminergic neurons

Project description:We directly reprogram human astrocytes (hIA) in vitro into induced dopaminergic neurons (iDAs). This process requires three transcription factors, NEUROD1, ASCL1 and LMX1A as well as one microRNA, mir218. This combined protocol gives rise to human astrocyte-derived iDAs with appropriate midbrain markers as defined by analyzing markers derived from human embryonic ventral midbrain samples at 7 and 9 weeks of age.

2017-03-27 | GSE93528 | GEO

Ventral mesencephalic dopaminergic (vmDA) precursors derived from human embryonic stem cells

Project description:Identify gene expression patterns between LMX1A+ and LMX1A- vmDA precurosrs derived from human embryonic stem cells (hESCs).

2021-07-19 | GSE171769 | GEO

experiment in midbrain primary cultures, enriched in dopaminergic neurons

Project description:To identify novel Nurr1 target genes we have used microarrays strategies in rat midbrain primary cultures, enriched in dopaminergic neurons, by the action of basic fibroblast growth factor (bFGF, 20ng/ml) and Sonic hedgedog (SHH), following upregulation of Nurr1 expression by depolarization.To this aim we have treated the cultures after 9 days in vitro for 2h with high KCl and collected 30 min or 2 h after the end of depolarization (2h + 30 min or 2h + 2h). With this experimental protocol we have identify a putative Nurr1 regulator and Nurr1 target Keywords: depolarization, microarrays, time course.

2007-03-19 | GSE4551 | GEO

Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons.

Project description:The direct conversion of fibroblasts to induced dopaminergic (iDA) neurons and other cell types demonstrates the plasticity of cell fate. The low efficiency of these relatively fast conversions suggests that kinetic barriers exist to safeguard cell-type identity. Here we show that suppression of p53, in conjunction with cell cycle arrest at G1 and appropriate extracellular environment, markedly increase the efficiency in the transdifferentiation of human fibroblasts to iDA neurons by Ascl1, Nurr1, Lmx1a and miR124. The conversion is dependent on Tet1, as G1 arrest, p53 knockdown or expression of the reprogramming factors induces Tet1 synergistically. Tet1 knockdown abolishes the transdifferentiation while its overexpression enhances the conversion. The iDA neurons express markers for midbrain DA neurons and have active dopaminergic transmission. Our results suggest that overcoming these kinetic barriers may enable highly efficient epigenetic reprogramming in general and will generate patient-specific midbrain DA neurons for Parkinson's disease research and therapy.

| S-EPMC4672381 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data