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Homo sapiens
734 Downloadable Samples
IlluminaHiSeq2500
Description
Cerebral organoids – three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells – have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. Overall design: 734 single-cell transcriptomes from human fetal neocortex or human cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Fetal neocortex data were generated at 12 weeks post conception (chip 1: 81 cells; chip 2: 83 cells) and 13 weeks post conception (62 cells). Cerebral organoid data were generated from dissociated whole organoids derived from induced pluripotent stem cell line 409B2 (iPSC 409B2) at 33 days (40 cells), 35 days (68 cells), 37 days (71 cells), 41 days (74 cells), and 65 days (80 cells) after the start of embryoid body culture. Cerebral organoid data were also generated from microdissected cortical-like regions from H9 embryonic stem cell derived organoids at 53 days (region 1, 48 cells; region 2, 48 cells) or from iPSC 409B2 organoids at 58 days (region 3, 43 cells; region 4, 36 cells).
Publication Title
Human cerebral organoids recapitulate gene expression programs of fetal neocortex development.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 44 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Many heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the of toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays.
Publication Title
Exposure to nickel, chromium, or cadmium causes distinct changes in the gene expression patterns of a rat liver derived cell line.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 15 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
In this report, we describe a successful protocol for isolating and expression-profiling live fluorescent- protein-labelled neurons from zebrafish embryos. As a proof-of-principle for this method, we FAC-sorted and RNA-profiled GFP-labelled spinal CiA interneurons and compared the expression profile of these cells to those of post-mitotic spinal neurons in general and to all trunk cells. We show that RNA of sufficient quality and quantity to uncover both expected and novel transcription profiles via Affymetrix microarray analysis can be extracted from 5,700 to 20,000 FAC-sorted cells. As part of this study, we also further confirm the genetic homology of mammalian and zebrafish V1 interneurons, by demonstrating that zebrafish V1 cells (CiAs) express genes that encode for the transcription factors Lhx1a and Lhx5. This protocol for dissociating, sorting and RNA-profiling neurons from organogenesis-stage zebrafish embryos should also be applicable to other developing organs and tissues and potentially other model organisms.
Publication Title
RNA profiling of FAC-sorted neurons from the developing zebrafish spinal cord.
Sample Metadata Fields
Age, Specimen part
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GSE3142- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Hair follicle matrix, outer root sheath, dermal papilla cells and melanocytes and a dermal fraction enriched in fibroblasts were FACS isolated from 4d backskins. Targets from two biological replicates of each were generated and the expression profiles were determined using Affymetrix Mouse Genechip 430A arrays. Comparisons between the sample groups allow the identification of cell-type specific genes.
Publication Title
Molecular dissection of mesenchymal-epithelial interactions in the hair follicle.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 146 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
The principal toxicity of acute organophosphate (OP) pesticides poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethalityparticularly through the inhibition of AChEstudies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms.
Publication Title
Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
The effects of BSE and 3-OABA on MDA-MB-231 cells were evaluated for effects on the whole transcriptome: including mRNAs and long intergenic non-coding RNA transcripts (lincRNA) using GeneChip Human Gene 2.1 ST Arrays by Affymetrix Inc.
Publication Title
Transcriptomic Profiling of MDA-MB-231 Cells Exposed to <i>Boswellia Serrata</i> and 3-O-Acetyl-B-Boswellic Acid; ER/UPR Mediated Programmed Cell Death.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human diffuse intrinsic pontine gliomas (DIPG) are an aggressive form of pediatric brain tumors that arise in the pons in young children thus resulting in significant morbidity and very poor survival. Recent data suggest that mutations in the histone H3.3 variant are often found in these tumors, though the mechanism of their contribution to oncogenesis remains to be elucidated. Here we report that the combination of constitutive PDGFRA activation and p53 suppression as well as expression of the K27M mutant form of the histone H3.3 variant leads to neoplastic transformation of hPSC-derived neural precursors. Our study demonstrates that human ES cells represent an excellent platform for the modeling of human tumors in vitro and in vivo, which could potentially lead to the elucidation of the molecular mechanisms underlying neoplastic transformation and the identification of novel therapeutic targets.
Publication Title
Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
The histone variant H3.3 is incorporated in a replication-independent manner at heterochromatic regions by the ATRX-DAXX histone chaperone complex. Here, we present a high-resolution x-ray crystal structure of an interaction surface between ATRX and DAXX. We used single amino acid substitutions in DAXX that abrogate formation of the complex to explore ATRX-dependent and -independent functions of DAXX. We found that the repression of specific murine endogenous retroviruses is dependent on DAXX, but not on ATRX. In support, we reveal the existence of two biochemically distinct DAXX-containing complexes: The ATRX-DAXX complex involved in gene repression and telomere chromatin structure, and a DAXX-SETDB1-KAP1-HDAC1 complex that represses endogenous retroviruses independently of ATRX and H3.3 incorporation into chromatin. We found that histone H3.3 stabilizes DAXX protein levels and affects DAXX-regulated genes independently of its incorporation into nucleosomes. Our findings represent the first description of a nucleosome-independent function for the H3.3 histone variant. Overall design: RNA-seq analysis of five embryonic stem cell lines in duplicate (Daxx-/- mESC, Daxx-/- mESC rescued with Daxx WT, H3.3 KO mESC, H3.3 KO mESC rescued with H3.3 WT and H3.3 L126A-L130A mutant)
Publication Title
Structural and mechanistic insights into ATRX-dependent and -independent functions of the histone chaperone DAXX.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 419 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
With aging, significant changes in circadian rhythms occur, including a shift in phase toward a morning chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here we employed a previously-described time-of-death analyses to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex (Brodmanns areas (BA) 11 and 47). Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ~10% of detected transcripts (p<0.05). Using a meta-analysis across the two brain areas, we identified a core set of 235 genes (q<0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than one thousand genes (1186 in BA11; 1591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep and mood in later life.
Publication Title
Effects of aging on circadian patterns of gene expression in the human prefrontal cortex.
Sample Metadata Fields
Sex, Age, Specimen part, Race
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