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RNA-Seq of GNRH1 neurons differentiated from human pluripotent stem cells (1)

ABSTRACT: This experiment was conducted to identify the transcriptome of human GNRH1 cells which has never been reported before and this experiment has identified some novel molecules which might regulate GNRH1 neuron differentiation which could be further explored to identify the origin and development of GNRH1 neurons in humans

INSTRUMENT(S): Sony SH800, NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Venkatram Yellapragada

PROVIDER: E-MTAB-8519 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells.

Lund Carina C Pulli Kristiina K Yellapragada Venkatram V Giacobini Paolo P Lundin Karolina K Vuoristo Sanna S Tuuri Timo T Noisa Parinya P Raivio Taneli T

Stem cell reports 20160714 2

Gonadotropin-releasing hormone (GnRH) neurons regulate human puberty and reproduction. Modeling their development and function in vitro would be of interest for both basic research and clinical translation. Here, we report a three-step protocol to differentiate human pluripotent stem cells (hPSCs) into GnRH-secreting neurons. Firstly, hPSCs were differentiated to FOXG1, EMX2, and PAX6 expressing anterior neural progenitor cells (NPCs) by dual SMAD inhibition. Secondly, NPCs were treated for 10 d ...[more]

PMID: 27426041

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RNA-Seq of GNRH1 neurons differentiated from human pluripotent stem cells (2)

Project description:This experiment was conducted to identify the transcriptome of human GNRH1 cells which has never been reported before and this experiment has identified some novel molecules which might regulate GNRH1 neuron differentiation which could be further explored to identify the origin and development of GNRH1 neurons in humans

2020-02-16 | E-MTAB-7956 | biostudies-arrayexpress

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Project description:This data would help in understanding the effect of FGF8 in the development of neurons critical for human puberty (GnRH neurons)

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Gene expression of A53T and corrected IPSC driven to DA neurons and exposed to paraquat and maneb

Project description:Parkinson disease (PD) is characterized by extensive loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). A strong association has been reported between PD and exposure to mitochondrial toxins such as the environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived, stem cell model of PD that allows comparison of -synuclein ( -syn) mutant cells and isogeneic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations specific to A53T -syn mutant A9-DA neurons (hNs). We report a novel molecular pathway whereby basal as well as toxin-induced oxidative and nitrosative stress inhibits the MEF2C-PGC1 transcription network in A53T hNs compared to corrected controls, contributing to mitochondrial dysfunction and apoptotic cell death. Our data provide mechanistic insight into gene-environmental interaction (GxE) in the pathogenesis of PD. Furthermore, using small molecule high-throughput screening, we identify the MEF2C-PGC1 pathway as a new drug target for therapeutic benefit in PD. In the current study, isogenic hiPSCs differing exclusively at a single amino acid (A53T) were exposed to either 2.8uM paraquat in combination with 1uM maneb for 24h or PBS vehicle control. Gene expression profile was analysed to assess the effect of both the genotype and exposure regiment on gene expression.

2013-12-05 | E-GEOD-46798 | biostudies-arrayexpress

Nociceptor differentiation from pluripotent cells

Project description:Here we performed the first combinatorial small molecule screen for the rapid conversion of hPSCs into postmitotic neurons. We identified a combination of five small molecule pathway inhibitors sufficient to yield neurons at > 75% efficiency within 10 days of differentiation in the absence of any recombinant growth factors. The resulting human neurons express canonical markers of nociceptive sensory fate. Two treatments (LSB and 3i) at days 2,3,5,7,9, and 15, in triplicate

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RNA-Seq profiling of dopaminergic neurons from iPSCs of Parkinson's disease patients

Project description:The fact that Parkinsons disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. In order to address this hypothesis, an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profiling was taken to advance our understanding of PD progression and the concordant downstream signaling pathways across divergent genetic predispositions. To model PD in vitro, neurons harboring disease-causing mutations were generated from patient-specific, induced pluripotent stem cells (iPSCs) and found to recapitulate several disease-related phenotypes. Signs of degeneration in PD midbrain dopaminergic (mDA) neurons were observed, reflecting the cardinal feature of PD. In addition, novel gene expression signatures were revealed for PD mDA neurons, providing molecular insights to disease phenotype observed in vitro, including oxidative stress vulnerability and altered neuronal activity. Notably, detailed transcriptome profiling of PD neurons showed that elevated RBFOX1, a gene previously linked to neurodevelopmental diseases, is responsible for a pattern of alternative RNA processing associated with PD-specific phenotypes in vitro.

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Transcriptome profiling of DA neurons, human midbrain-like organoids and prenatal midbrain

Project description:Recent advances in three dimensional (3D) culture systems have led to the generation of brain organoids that share resemblance to different parts of the human brains; however, a 3D organoid model of the midbrain that contains functional midbrain dopaminergic (mDA) neurons has not been reported. In this study, we develop a method to differentiate human PSCs into a large multicellular organoid-like structure that contains distinct layers of neuronal cells with a transcriptomic profile that resembles human prenatal midbrain. Importantly, we detected electrically active and functionally mature mDA neurons, and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using non-3D methods or in the MLOs generated from mouse embryonic stem cells, our human MLOs uniquely produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a novel tractable in vitro system to study the human midbrain and its related diseases.

2016-08-24 | E-MTAB-4868 | biostudies-arrayexpress

Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_human]

Project description:TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3â?? untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents RNA-seq sample(s).

2016-07-05 | E-GEOD-77702 | biostudies-arrayexpress

Transcriptional profiling of human naive embryonic stem cells

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2016-03-01 | E-MTAB-4461 | biostudies-arrayexpress

Selective Death in Spinal Muscular Atrophy: Genome-Wide RNA-Seq Using Purified Patient-Derived Motor Neurons

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