Ventral mesencephalic dopaminergic (vmDA) precursors derived from human embryonic stem cells
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ABSTRACT:
PROVIDER: PRJNA720859 | ENA |
REPOSITORIES: ENA
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Project description:Identify gene expression patterns between LMX1A+ and LMX1A- vmDA precurosrs derived from human embryonic stem cells (hESCs).
2021-07-19 | GSE171769 | GEO
Project description:The mesencephalic dopaminergic (mDA) cell system is composed by two major groups of projecting cells in the Substantia Nigra (A9 neurons) and the Ventral Tegmental Area (A10 cells). A9 neurons form the nigrostriatal pathway and are involved in regulating voluntary movements and postural reflexes. Their selective degeneration leads to Parkinsons disease (PD). We used cDNA microarrays and nanoCAGE technology coupled with Laser Capture Microdissection (LCM) to characterize the intrinsic physiological properties of A9 DA neurons. Surprisingly, we found that these cells express alpha- and beta- chains of haemoglobin. Here we report that globin-immunoreactivity decorates the majority of A9 DA neurons, a subpopulation of cortical and hippocampal astrocytes as well as mature oligodendrocytes. This pattern of expression was confirmed in different mouse strains, in rat and human. This is the first report showing that haemoglobin is expressed in the Substantia Nigra of human post mortem brain. Our data suggest that the most famed oxygen-carrying globin is not exclusively restricted to the blood, but it may play a role in the normal physiology of the brain as well as in neurodegenerative disorders. To investigate the biological effects of globin expression, alpha- and beta- chains of mouse hemoglobin were overexpressed in MN9D dopaminergic neuroblastoma cell lines. RNA from 4 replicates each of over-expressing cells and of control samples, for a total of 8 samples, were hybridized on Affymetrix GeneChip Mouse Genome 430A 2.0 Arrays. Hybridization of one of the control samples did not pass quality assessment and the sample was therefore excluded from further analysis.
2010-02-25 | E-GEOD-16192 | biostudies-arrayexpress
Project description:The mesencephalic dopaminergic (mDA) cell system is composed by two major groups of projecting cells in the Substantia Nigra (A9 neurons) and the Ventral Tegmental Area (A10 cells). A9 neurons form the nigrostriatal pathway and are involved in regulating voluntary movements and postural reflexes. Their selective degeneration leads to Parkinson’s disease (PD). We used cDNA microarrays and nanoCAGE technology coupled with Laser Capture Microdissection (LCM) to characterize the intrinsic physiological properties of A9 DA neurons. Surprisingly, we found that these cells express alpha- and beta- chains of haemoglobin. Here we report that globin-immunoreactivity decorates the majority of A9 DA neurons, a subpopulation of cortical and hippocampal astrocytes as well as mature oligodendrocytes. This pattern of expression was confirmed in different mouse strains, in rat and human. This is the first report showing that haemoglobin is expressed in the Substantia Nigra of human post mortem brain. Our data suggest that the most famed oxygen-carrying globin is not exclusively restricted to the blood, but it may play a role in the normal physiology of the brain as well as in neurodegenerative disorders.
2009-08-04 | GSE16192 | GEO
Project description:RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain Murine midbrain dopaminergic neurons from the SNpc and VTA regions
2015-07-27 | E-GEOD-64452 | biostudies-arrayexpress
Project description:RFX3 and RFX4 were defined as transcription factors (TFs) with enriched TF binding sites in cis-regulatory elements that are activated during the conversion of human embryonic stem cells (hESCs) into ventral telencephalic MGE-like patterned neuronal precursors. Therefore, we conducted CRISPRi-mediated knockdown of RFX3 or RFX4 and profiled changes in gene expression in MGE-like ventral telencephalic progenitors by RNA-seq. This analysis revealed that RFX3 and RFX4 play important roles in cortical interneuron development, specifically during the transition from mitotically cycling neuronal precursors into post mitotic neurons.
2024-04-18 | GSE239413 | GEO
Project description:Ventral midbrain (VM) dopaminergic progenitor cells derived from human pluripotent stem cells have the potential to replace endogenously lost dopamine neurons and are currently in preclinical and clinical development for treatment of Parkinson’s Disease (PD). However, one main challenge in the quality control of the cells is that rostral and caudal VM progenitors are extremely similar transcriptionally though only the caudal VM cells give rise to dopaminergic neurons with functionality in PD. Therefore, it is critical to develop assays which can rapidly and reliably discriminate rostral from caudal VM cells during clinical manufacturing. Here, we applied shotgun proteomics to search for novel secreted biomarkers specific for caudal VM progenitors compared to rostral VM progenitors and validated key hits by ELISA. From this, we identified novel secreted markers (CPE, LGI1 and PDGFC) significantly enriched in caudal versus rostral VM progenitor cultures, whereas the markers CNTN2 and CORIN were significantly enriched in rostral VM cultures. With this data, we suggest and test in clinical grade samples a panel of coupled ELISA assays that can be applied as a quality control tool for assessing the correct patterning of cells during clinical manufacturing.
2023-12-13 | PXD039510 | Pride
Project description:The cardinal clinical features of Parkinson's disease result from selective loss of midbrain dopaminergic neurons. The goal of this experiment is to determine the gene expression profiles of these neurons by studying untreated rat substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopaminergic neurons using laser capture microscopy to obtain region-specific neuronal mRNA.
2007-10-27 | E-GEOD-1157 | biostudies-arrayexpress
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Project description:Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks and protects dopaminergic neurons against apoptosis. RNA-seq data for differentially expressed genes in the SNpc of En1+/- mice, En2 infused mice and 6-OHDA/En2 injection experiments.
2015-09-24 | E-GEOD-72321 | biostudies-arrayexpress
Project description:Pitx3 is a transcription factor that is expressed in all midbrain dopaminergic (mDA) neurons during early development, but later becomes restricted in dopaminergic subsets of substantia nigra compacta (SNc) and of the ventral tegmental are (VTA) that are vulnerable to neurodegenerative stress (MPTP, 6-OHDA, rotenone, Parkinson's disease). Overall, in mice, Pitx3 is required for developmental survival of ventral SNc neurons and for postnatal survival of VTA neurons (after postnatal day 40). With the aim of determining the gene networks that distinguish Pitx3-vulnerable (Pitx3-positive) from Pitx3-resistant (Pitx3-negative) subsets of SNc and VTA, we performed a comparison at the transcriptome level between FAC-sorted mDA neurons of SNc and VTA that were obtained from wild-type and Pitx3-/- newborn mice. The latter mice have already lost the majority of their TH+Calb1- mDA neurons of ventral SNc (Pitx3-dependent), but their TH+Calb1+ neurons of dorsal SNc (Pitx3-independent), including all of VTA neurons (50% are Pitx3-dependent and 50% Pitx3-independent), are unaffected by Pitx3 deletion. At postnatal day 40, Pitx3-/- mice display a marked loss of dopaminergic subsets of VTA that normally co-express Pitx3 and Calb1 (Pitx3-dependent neurons of VTA).
2016-01-31 | GSE75777 | GEO