Although many distinct mutations in a variety of genes are known to cause Amyotrophic Lateral Sclerosis (ALS), it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neural degeneration. Here, we have combined reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing to define the transcriptional changes that are induced in human motor neurons by mutant SOD1. Mutant SOD1 protein induced a transcriptional signature indicative of increased oxidative stress, reduced mitochondrial function, altered sub-cellular transport as well as activation of the ER stress and unfolded protein response pathways. Functional studies demonstrated that perturbations in these pathways were indeed the source of altered transcript levels. Overall design: 5 samples, 2 patient-derived SOD1A4V and 3 isogenic control samples where the mutation has been corrected. All samples are motor neurons derived from induced pluripotent stem cells (iPSCs), and isolated after lentiviral infection with an Hb9:RFP construct and FACS purification. Each sample is a separate biological replicate.
Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative epigenomic analysis of murine and human adipogenesis.
Sex, Specimen part
View SamplesHuman abdominal adipose tissue was obtained with informed consent from a 33-year old Caucasian female (BMI = 32.96 Kg/m2) undergoing lipoaspiration. Adipose stromal cells (hASCs) were isolated and differentiated into adipocytes in vitro.
Comparative epigenomic analysis of murine and human adipogenesis.
Sex, Specimen part
View SamplesBiofilm formation and type III secretion have been shown to be reciprocally regulated in P. aeruginosa, and it has been suggested that factors related to acute infection may be incompatible
Biofilms and type III secretion are not mutually exclusive in Pseudomonas aeruginosa.
No sample metadata fields
View Samplesgene expression data from mouse adipocyte, with and without Ebf1 knock-down
Early B-cell factor-1 (EBF1) is a key regulator of metabolic and inflammatory signaling pathways in mature adipocytes.
Specimen part
View Samples3T3-L1 pre-adipocyte cells were grown to confluence and induced to differentiate in adipogeneic media.
Comparative epigenomic analysis of murine and human adipogenesis.
Specimen part
View SamplesGene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measured the gene expression dynamics of retinoic acid driven mESC differentiation using an unbiased single-cell transcriptomics approach. We found that the exit from pluripotency marks the start of a lineage bifurcation as well as a transient phase of susceptibility to lineage specifying signals. Our study revealed several transcriptional signatures of this phase, including a sharp increase of gene expression variability and a handover between two classes of transcription factors. In summary, we provide a comprehensive analysis of lineage commitment at the single cell level, a potential stepping stone to improved lineage control through timing of differentiation cues. Overall design: Bulk and single-cell RNA-seq (SCRB-seq and SMART-seq) of mouse embryonic stem cells after different periods of continuous exposure to retinoic acid. Bulk RNA-seq of cell lines derived after retinoic exposure and after differentiation with retinoic acid and MEK inhibitor combined.
Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells.
Cell line, Subject
View SamplesTwo 96-well plates per genotype wild type and Myd88 knockout, 4 hour time series in 0.5 hr increments Overall design: Myd88 BMDM transcriptional profiling to complement TF-seq data
Simultaneous Pathway Activity Inference and Gene Expression Analysis Using RNA Sequencing.
Sex, Age, Specimen part, Cell line, Treatment, Subject, Time
View SamplesBone marrow derived macrophages treated with small molecules and stimulated with LPS Overall design: Wild-type BMDMs pretreated with small molecules for 30 minutes prior to stimulation with LPS
Simultaneous Pathway Activity Inference and Gene Expression Analysis Using RNA Sequencing.
Sex, Age, Specimen part, Cell line, Treatment, Subject, Time
View SamplesBone marrow derived macrophages treated with small molecules and stimulated with LPS Overall design: Wild-type BMDMs pretreated with small molecules for 30 minutes prior to stimulation with LPS
Simultaneous Pathway Activity Inference and Gene Expression Analysis Using RNA Sequencing.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View Samples