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SRP134044
Homo sapiens
18 Downloadable Samples
Illumina HiSeq 2000
Description
Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. We cultured cells in uniform conditions and profiled genome-wide copy numbers, mRNAs, proteins and protein turnover rates in each cell line. We discovered substantial heterogeneity between HeLa variants, especially between lines of the CCL2 and Kyoto varieties, and observed progressive divergence within a specific cell line over 50 successive passages. Genomic variability has a complex, nonlinear effect on transcriptome, proteome and protein turnover profiles, and proteotype patterns explain the varying phenotypic response of different cell lines to Salmonella infection. These findings have implications for the interpretation and reproducibility of research results obtained from human cultured cells. Overall design: Multi-omic (genome, transcriptome, proteome, protein turnover) analysis of 14 HeLa cell lines obtained from different laboratories but grown under the same conditions.
Publication Title
Multi-omic measurements of heterogeneity in HeLa cells across laboratories.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Wnt signaling potentiates nevogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Melanocytes within benign human nevi are the paradigm for tumor suppressive senescent cells in a pre-malignant neoplasm. These cells typically contain mutations in either the BRAF or N-RAS oncogene and express markers of senescence, including p16. However, a nevus can contain 10s to 100s of thousands of clonal melanocytes and approximately 20-30% of melanoma are thought to arise in association with a pre-existing nevus. Neither observation is indicative of fail-safe senescence-associated proliferation arrest and tumor suppression. We set out to better understand the status of nevus melanocytes. Proliferation-promoting Wnt target genes, such as cyclin D1 and c-myc, were repressed in oncogene-induced senescent melanocytes in vitro, and repression of Wnt signaling in these cells induced a senescent-like state. In contrast, cyclin D1 and c-myc were expressed in many melanocytes of human benign nevi. Specifically, activated Wnt signalling in nevi correlated inversely with nevus maturation, an established dermatopathological correlate of clinical benignancy. Single cell analyses of lone epidermal melanocytes and nevus melanocytes showed that expression of proliferation-promoting Wnt targets correlates with prior proliferative expansion of p16-expressing nevus melanocytes. In a mouse model, activation of Wnt signaling delayed, but did not bypass, senescence of oncogene-expressing melanocytes, leading to massive accumulation of proliferation-arrested, p16-positive non-malignant melanocytes. We conclude that clonal hyperproliferation of oncogene-expressing melanocytes to form a nevus is facilitated by transient delay of senescence due to activated Wnt signaling. The observation that activation of Wnt signaling correlates inversely with nevus maturation, an indicator of clinical benignancy, supports the notion that persistent destabilization of senescence by Wnt signaling contributes to the malignant potential of nevi.
Publication Title
Wnt signaling potentiates nevogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- NextSeq 500
Description
The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury. Overall design: We generated transciptome data from proliferative cardiac cells collected from 3, 7 or 14 days following myocardial infarction (MI) or sham surgery. This series includes single-cell transcriptome data from (Ki67-RFP+) cardiac cells collected from neonatal murine hearts, adult homeostatic murine hearts or adult murine hearts collected 14 days following myocardial infarction (MI), ischemic/perfusion (I/R) or sham surgery.
Publication Title
Profiling proliferative cells and their progeny in damaged murine hearts.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The aim of this study was to determine the effects of TGF at the premalignant stage of CRC development.
Publication Title
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Colorectal cancer can be divided into four consensus molecular subtypes, which might associate with distinct precursor lesions. The aim of this study was to determine the subtype affiliation of two types of colorectal adenomas: tubular adenomas (TAs) and sessile serrated adenomas (SSAs) and to determine the activity of TGF signaling and the role of this cytokine in subtype affiliation.
Publication Title
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaGenomeAnalyzerII, IlluminaHiSeq2000
Description
We applied deep-sequencing based technique, 3''-Seq, to obtain comprehansive maps of poly-A sites in human cells. 3''-Seq was applied to two cell lines (U2OS and RPE-1), in control and PABPN1 knockdown cells Overall design: Examination of poly-A sites in control and PABPN1kd cells (in two different cell lines)
Publication Title
The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 116 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This series analyses germinating Arabidopsis seeds with both temporal and spatial detail, revealing two transcriptional phases that are separated with respect to testa rupture. Performed as part of the ERA-NET Plant Genomics grant vSEED.
Publication Title
Transcriptional dynamics of two seed compartments with opposing roles in Arabidopsis seed germination.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 16 Downloadable Samples
- NextSeq 500
Description
Adult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated single cell transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from
Publication Title
Tubuloids derived from human adult kidney and urine for personalized disease modeling.
Sample Metadata Fields
Specimen part, Subject
View Samples