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Homo sapiens
2 Downloadable Samples
IlluminaHiSeq2000
Description
Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated in the pathogenesis of common late-onset disorders, but it is not clear how they arise and propagate in the humans. Here we show that mtDNA mutations are present in primordial germ cells (PGCs) within healthy female human embryos. Close scrutiny revealed the signature of selection against non-synonymous variants in the protein-coding region, tRNA gene variants, and variants in specific regions of the non-coding D-loop. In isolated single PGCs we saw a profound reduction in the cellular mtDNA content, with discrete mitochondria containing ~5 mtDNA molecules during early germline development. Single cell deep mtDNA sequencing showed rare variants reaching higher heteroplasmy levels in later PGCs, consistent with the observed genetic bottleneck, and predicting >80% levels within isolated organelles. Genome-wide RNA-seq showed a progressive upregulation of genes involving mtDNA replication and transcription, linked to a transition from glycolytic to oxidative metabolism. The metabolic shift exposes deleterious mutations to selection at the organellar level during early germ cell development. In this way, the genetic bottleneck prevents the relentless accumulation of mtDNA mutations in the human population predicted by Muller's ratchet. Mutations escaping this mechanism will, however, show massive shifts in heteroplasmy levels within one human generation, explaining the extreme phenotypic variation seen in human pedigrees with inherited mtDNA disorders. Overall design: RNA-Seq and NGS analysis to investigate transcriptomes and mtDNA sequences of fetal hPGCs
Publication Title
Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos.
Sample Metadata Fields
No sample metadata fields
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SRP157750- Homo sapiens
- 39 Downloadable Samples
- NextSeq 500
Description
The Alternative Lengthening of Telomeres (ALT) pathway stimulates telomere elongation and prevents cellular senescence in approximately 60% of osteosarcoma. While the precise mechanisms underlying the ALT pathway are unclear, mutations in the chromatin remodeling protein ATRX, histone chaperone DAXX, and the histone variant H3.3, correlate with ALT status. ATRX and DAXX facilitate deposition of the histone variant H3.3 within heterochromatic regions including the telomere suggesting that loss of ATRX, DAXX, and/or H3.3 lead to defects in heterochromatin maintenance at telomeres, ultimately contributing to ALT activity. Previous studies have detected genetic mutations in ATRX, DAXX, and H3.3 in ALT cell lines and tumor samples. However, a subset of ALT samples show loss of ATRX or DAXX protein expression or localization without evidence of genetic alterations, indicating a role for other defects in ATRX/DAXX/H3.3 function. Here, using Next Generation Sequencing, we identified a novel gene fusion event between DAXX and the kinesin motor protein, KIFC3, which leads to the translation of a chimeric DAXX-KIFC3 fusion protein. Here, we demonstrate that the fusion of KIFC3 to DAXX leads to defects in DAXX function and likely perpetuates ALT activity. These data highlight a previously unrecognized mechanism of DAXX inactivation in ALT positive osteosarcoma and provide rationale for thorough and comprehensive analyses of ATRX/DAXX/H3.3 proteins in ALT positive cancers. Overall design: 13 cell lines sequenced in triplicate, totaling 39 sequencing samples
Publication Title
Identification of a novel gene fusion in ALT positive osteosarcoma.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Previous studies have reported that human pluripotent stem cells (hPSCs) generate dorsal forebrain, cortical-like neurons under default differentiation in the absence of patterning morphogens. Novel bioinformatic analyses of whole transcriptome data allow us to examine these cells' regional specification more comprehensively. Furthermore, these tools allow us to ask how well hPSNs mimic their endogenous counterparts during various stages of in vivo human brain development.
Publication Title
Default Patterning Produces Pan-cortical Glutamatergic and CGE/LGE-like GABAergic Neurons from Human Pluripotent Stem Cells.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Ovis aries
- 4 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Reverse genetics has been widely used to investigate function of viral genes. In the present study we investigated the gene expression profile of a primary ovine cell (OFTu) in response to infection with the wild type (OV-IA82) and deletion mutant virus (OV-IA82024) aiming to determine possible functions for ORFV024 during ORFV infection.
Publication Title
A novel inhibitor of the NF-{kappa}B signaling pathway encoded by the parapoxvirus orf virus.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 160 Downloadable Samples
- NextSeq 500
Description
We present ScarTrace, a single-cell sequencing strategy that allows us to simultaneously quantify information on clonal history and cell type for thousands of single cells obtained from different organs from adult zebrafish. Using this approach we show that all blood cells types in the kidney marrow arise from a small set of multipotent embryonic. In contrast, we find that cells in the eyes, brain, and caudal tail fin arise from many embryonic progenitors, which are more restricted and produce specific cell types in the adult tissue. Next we use ScarTrace to explore when embryonic cells commit to forming either left or right organs using the eyes and brain as a model system. Lastly we monitor regeneration of the caudal tail fin and identify a subpopulation of resident macrophages that have a clonal origin that is distinct from other blood cell types. Overall design: Single cell sequencing data from cells isolated from zebrafish organs (whole kidney marrow, forebrain, hindbrain, left eye, right eye, left midbrain, right midbrain, and regenerated fin). For each cell, we provide libraries with transcritpome and with clonal information, respectively.
Publication Title
Whole-organism clone tracing using single-cell sequencing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 63 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of uterine microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchestrated the immune reponse triggered in presence of embryo
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of B16 tumor microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchastrated the immune reponse triggered in presence of tumors
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of uterine microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchestrated the immune reponse triggered in presence of embryo.
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
We report the total RNA-seq results after CDK9, CDK12 and CDK13 depletion in human HCT116 cells for three days. RNA-seq was performed in cells using two non-targeting replicates and two different shRNAs for each CDK knockdown. For each CDK knockdown, most of the differentially expressed genes were down-regulated with a very small subset of genes upregulated. Different CDK proteins control distinct subsets of genes in vivo, with CDK12 and CDK13 sharing more overlap in function compared to CDK9. Besides, CDK12 and CDK13 loss preferentially affects DNA damage response and snRNA gene expression, respectively. Overall design: Examine the changes of mRNA expression levels after CDK9, CDK12 and CDK13 depletion.
Publication Title
Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processing.
Sample Metadata Fields
No sample metadata fields
View Samples