Filters
Technology
Platform
SRP070060
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
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The ectopic expression of a Col10a1-13del transgene in osteocytes induced ER stress, compromising their differentiation and expression of Sclerostin, resulting in generalized bone overgrowth resembling human crainodiaphyseal chondrodysplasia (CCD).
Publication Title
Activating the unfolded protein response in osteocytes causes hyperostosis consistent with craniodiaphyseal dysplasia.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We compared transcriptome profile of ITox2C strain expressing dCas9-VP64 (aka screen strain) that express gRNA 9-1 with those expressing no gRNA Overall design: mRNA profiles of Saccharomyces cerevisiae W303 expressing SNCA and dCas9-VP64 (screen strain) with gRNA 9-1 or no gRNA (negative control) were generated by deep sequencing, in duplicates, using Illumina HiSeq.
Publication Title
Randomized CRISPR-Cas Transcriptional Perturbation Screening Reveals Protective Genes against Alpha-Synuclein Toxicity.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 294 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 150 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study was conducted in order to identify biomarkers for a prognostic gene expression signature for metastases in early stage CRC.
Publication Title
A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Transcriptome analysis of RNAs extracted from 2 hour-TGF-b-treated or untreated LX-2 cells with or without STAT3 knockdown
Publication Title
Transforming Growth Factor-β (TGF-β) Directly Activates the JAK1-STAT3 Axis to Induce Hepatic Fibrosis in Coordination with the SMAD Pathway.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of RNAs extracted from livers of wild type or Smurf1 knock out (KO) or Smurf2 KO mice at age of 11 month old.
Publication Title
Non-proteolytic ubiquitin modification of PPARγ by Smurf1 protects the liver from steatosis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
The pulmonary alveolar epithelium which play key role in lung biological function is mainly composed of two types of epithelial cells: alveolar type I (AT1) and type II (AT2) cells. We know very little about developmental heterogeneity of the AT1 cell population. By using 10X genomics “Chromium Single Cell” technology, we performed single-cell RNA-seq (scRNA-seq) analyses of AT1 cells at postnatal day 3 (P3), P15, and P60, along with AT2 cells (P60) in mice. Our study identified a robust new genetic marker (Igfbp2) of postnatal AT1 cells. The study also provided the transcriptome information of AT1 cells during alveologensis. Overall design: We performed 10X genomics single-cell RNA-seq at various developmental stages of AT1 cells of lungs at postnatal (P)3, P15, and P60. We also performed 10X genomics single-cell RNA-seq of AT2 cells of P60 lungs.
Publication Title
Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
MECP2 duplication syndrome, a childhood neurological disorder characterized by autism, intellectual disability, motor dysfunction, anxiety and epilepsy, is caused by a duplication on chromosome Xq28 spanning the MECP2 gene that results in doubling of MeCP2 levels. MECP2 overexpression in mice causes neurobehavioral and electroencephalographic defects similar to those of human patients, but the gross anatomy of the brain remains unaffected. We hypothesized that MECP2 duplication syndrome would be reversible and tested two methods to restore MeCP2 levels to normal: conditional genetic recombination and antisense oligonucleotide therapy. Both approaches rescued molecular, physiological and behavioral features of adult symptomatic mice. Antisense therapy also restored normal MeCP2 levels in lymphoblastoid cells from MECP2 duplication patients, in a dose-dependent manner. Our data indicate that antisense oligonucleotides could provide a viable therapeutic approach for human MECP2 duplication syndrome as well as other disorders involving copy number gains. Overall design: Hippocampal mRNA profiles of conditional MECP2 overexpression and genetic rescue mice were generated by deep sequencing, in triplicate, using Illumina TruSeq.
Publication Title
Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
MECP2 duplication syndrome, a childhood neurological disorder characterized by autism, intellectual disability, motor dysfunction, anxiety and epilepsy, is caused by a duplication on chromosome Xq28 spanning the MECP2 gene that results in doubling of MeCP2 levels. MECP2 overexpression in mice causes neurobehavioral and electroencephalographic defects similar to those of human patients, but the gross anatomy of the brain remains unaffected. We hypothesized that MECP2 duplication syndrome would be reversible and tested two methods to restore MeCP2 levels to normal: conditional genetic recombination and antisense oligonucleotide therapy. Both approaches rescued molecular, physiological and behavioral features of adult symptomatic mice. Antisense therapy also restored normal MeCP2 levels in lymphoblastoid cells from MECP2 duplication patients, in a dose-dependent manner. Our data indicate that antisense oligonucleotides could provide a viable therapeutic approach for human MECP2 duplication syndrome as well as other disorders involving copy number gains. Overall design: Hippocampal mRNA profiles of WT, MECP2-TG and MECP2-TG ASO-treated treated mice 8 weeks after the initiation of the treatment, were generated by deep sequencing, in triplicate, using Illumina TruSeq.
Publication Title
Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides.
Sample Metadata Fields
No sample metadata fields
View Samples