Differential expression between floor plate and ventral lateral region in E10.5 mouse embryo midbrain
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE25178 | GEO | 2011/05/18
SECONDARY ACCESSION(S): PRJNA134441
REPOSITORIES: GEO
Similar Datasets
Project description:The data revealed differential expression between floor plate and ventral lateral region in E10.5 mouse embryo midbrain. Several differentially expressed genes in these regions have been reported in the literature, demonstrating reliability of tissue dissection. Midbrain floor plate and non-overlapping adjacent ventral lateral region of mouse E10.5 embryo midbrain was dissected. Each sample was a pool from 6 embryos. Three replicates for each region were used for the experiment.
2011-05-18 | E-GEOD-25178 | biostudies-arrayexpress
Project description:Human pluripotent stem cells (hPSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of hPSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However the effective use of hPSCs for cell therapy has lagged far behind. While mouse PSC-derived DA neurons have shown efficacy in models of Parkinson’s disease, DA neurons derived from human PSCs generally display poor in vivo performance. There are also considerable safety concerns for hPSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor plate-based strategy for the derivation of human DA neurons that efficiently engraft, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor plate precursors are derived from hPSCs in days following exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signaling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive in vitro molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of hPSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in PD animal models in three host species. Long-term engraftment in 6-OHDA-lesioned mouse and rats demonstrates robust survival of midbrain DA neurons, complete restoration of amphetamine-induced rotation behavior and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into Parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models tested indicate considerable promise for the development of cell based therapies in PD.
2011-11-07 | GSE32658 | GEO
Project description:Human pluripotent stem cells (hPSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of hPSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However the effective use of hPSCs for cell therapy has lagged far behind. While mouse PSC-derived DA neurons have shown efficacy in models of Parkinson’s disease, DA neurons derived from human PSCs generally display poor in vivo performance. There are also considerable safety concerns for hPSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor plate-based strategy for the derivation of human DA neurons that efficiently engraft, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor plate precursors are derived from hPSCs in days following exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signaling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive in vitro molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of hPSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in PD animal models in three host species. Long-term engraftment in 6-OHDA-lesioned mouse and rats demonstrates robust survival of midbrain DA neurons, complete restoration of amphetamine-induced rotation behavior and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into Parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models tested indicate considerable promise for the development of cell based therapies in PD. Differentiated hESC with three conditions (LSB, LSB/S/F8, LSB/S/F8/CHIR) were subjected to RNA extraction in specific timepoint (day 0, 1, 3, 5, 7, 11, 13, 25) and hybridization on Illumina microarrays. Each sample has 3 or 4 biological repeats. Based on previous study* of dual SMAD inhibition neural induction, we developed new midbrain dopamine neuron protocol. It depends on time specific treatment of below factors (LSB/S/F8/CHIR): L (LDN193189 (BMP inhibitor) , day 0-11), SB (SB431542 (TGF-b signal inhibitor), day 0-5), S (SHH + Purmorphamine (Smo agonist), day 1-7), F8 (FGF8, day 1-7) and CHIR (CHIR99021 (GSK3b inhibitor), day 3-13) LSB and LSB/S/F8 are limited control conditions of dual SMAD only (LSB) or traditional patterning with Sonic and FGF (LSB/S/F8) *Chambers,S.M. et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat. Biotechnol. 27, 275-280 (2009).
2011-11-07 | E-GEOD-32658 | biostudies-arrayexpress
Project description:Regional specificity of stem cell-derived astrocytes is believed to be an important prerequisite for their applications in disease modelling and cell-based therapies. The regional identity of these astrocytes is often defined by the positional characteristics of their antecedent, stem cell-derived neural progenitors patterned to a fate of interest, with the assumption that the positional specification is to be preserved by the derived astrocytes. Using a human iPSC line designed for tracing midbrain floor plate derivatives, here we show that lineage composition of the derived astrocytes is not a faithful recapitulation of the founder progenitor population, as demonstrated by the loss of floor plate differentiated progeny in the final astrocyte products. Using deep single cell RNA sequencing, we identified distinct transcriptomic signatures of midbrain floor plate-derived astrocytes. Our study highlights the need for rigorous characterisation of PSC-derived regional astrocytes and provides a valuable resource for assessing midbrain floor plate-derived human astrocytes.
2024-09-24 | GSE252624 | GEO
Project description:Floor plate-derived extracellular signaling molecules, including canonical axon guidance cues of the Netrin family, control neuronal circuit organization. Despite the importance of the floor plate as an essential signaling centre in the developing vertebrate central nervous system, no systematic approach to identify binding partners for floor plate-expressed cellsurface and secreted proteins has been carried out. Here, we used a high-throughput assay to discover extracellular protein-protein interactions, which likely take place in the zebrafish floor plate microenvironment. The assembled floor plate network contains 47 interactions including the hitherto not reported interaction between Netrin-1 and Draxin. We further characterized this interaction, narrowed down the binding interface, and demonstrated that Draxin competes with Netrin receptors for binding to Netrin-1. Our results suggest that Draxin functions as an extracellular Netrin signaling modulator in vertebrates. A reciprocal gradient of Draxin might shape or sharpen the active Netrin gradient, thereby critically modulating its effect.
2015-05-31 | E-MTAB-3609 | biostudies-arrayexpress
Project description:Embryonic stem (ES) cells were differentiated in culture to midbrain dopaminergic (mDA) progenitors and subjected to ChIP-seq analysis to resolve genome-wide binding sites of forkhead box protein A2 (Foxa2). Foxa2 was found to directly regulate multiple lineage pathways to specify midbrain dopaminergic and floor plate progenitor identity.
2012-07-01 | E-MTAB-1137 | biostudies-arrayexpress
Project description:The circadian nature of mood and its dysfunction in affective disorders is well recognized, but the underlying molecular mechanisms are still unclear. We showed that the circadian nuclear receptor REV-ERBa, which is associated with bipolar disorder, impacts midbrain dopamine production and mood-related behavior in mice. Genetic deletion of the Rev-erba gene or pharmacological inhibition of REV-ERBa activity in the ventral midbrain induced mania-like behavior in association with a central hyperdopaminergic state. We used microarrays to identify differentially expressed genes in the ventral midbrains of wild-type (WT) and Rev-erba knock-out (RKO) mice.
2014-02-19 | GSE55119 | GEO
Project description:The circadian nature of mood and its dysfunction in affective disorders is well recognized, but the underlying molecular mechanisms are still unclear. We showed that the circadian nuclear receptor REV-ERBa, which is associated with bipolar disorder, impacts midbrain dopamine production and mood-related behavior in mice. Genetic deletion of the Rev-erba gene or pharmacological inhibition of REV-ERBa activity in the ventral midbrain induced mania-like behavior in association with a central hyperdopaminergic state. We used microarrays to identify differentially expressed genes in the ventral midbrains of wild-type (WT) and Rev-erba knock-out (RKO) mice. Male RKO and WT mice (10-15 weeks of age) were maintained in a C57BL/6J background. Mice were housed in temperature-controlled (22-23ºC) quarters under a 12-h light-dark (LD) photoperiod (lights on at 8:00 a.m.). After entrainment for >10 days under LD conditions, mice were kept in constant darkness (DD) for 2 days starting at lights-off time. On the third day, mice were sacrificed at indicated time points by cervical dislocation.
2014-02-19 | E-GEOD-55119 | biostudies-arrayexpress
Project description:single-cell RNA sequencing data (plate-based CelSeq2) of developing mouse ventral midbrain GABAergic neurons. vmbGABA series contains E16 and P0 VGAT mouse ventral midbrain and E16 and P0 VGAT/PITX3 co-expressing mouse ventral midbrain.
2024-10-08 | GSE268378 | GEO