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GSE102444
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Respiratory innate immunity requires alveolar macrophages, which are specifically targeted by the S. aureus toxin alpha toxin. These data compare the response of alveolar macrophages to S. aureus with or without alpha toxin neutralization.
Publication Title
S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Patients with bicuspid aortic valve (BAV) have increased risk of thoracic ascending aortic aneurysm (AscAA) and dissection compared to those with a normal tricuspid aortic valve (TAV). The present study was undertaken to evaluate whether differences in gene expression exist in aortas from BAV and TAV patients with AscAA.
Publication Title
Elevated expressions of osteopontin and tenascin C in ascending aortic aneurysms are associated with trileaflet aortic valves as compared with bicuspid aortic valves.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Long non-coding RNA (lncRNA) have been implicated in human pathology, however, their roles in colorectal carcinogenesis has not been fully elucidated. In the current study, whole-transcriptome was analyzed in 3 pairs of colorectal cancer (CRC) and matched normal mucosa (NM) by RNA sequencing (RNA-seq). Followed by confirmation using the Cancer Genome Atlas (TCGA) dataset, we identified 27 up-regulated and 22 down-regulated lncRNAs in CRC. Up-regulation of four lncRNAs, hereby named colorectal cancer associated lncRNA (CRCAL)-1 [AC021218.2], CRCAL-2 [LINC00858], CRCAL-3 [RP11-138J23.1] and CRCAL-4 [RP11-435O5.2], was further validated by real-time RT-PCR in 139 colorectal neoplasms and matched NM tissues. Knockdown of CRCAL-3 and CRCAL-4 in colon cancer cells reduced cell viability and colony formation ability, and induced cell cycle arrest. TCGA dataset supported the associations of CRCAL-3 and CRCAL-4 with cell cycle and revealed a co-expression network comprising dysregulated lncRNAs associated with protein-coding genes. In conclusion, RNA-seq identified numbers of novel lncRNAs dysregulated in CRC. In vitro experiments and GO term enrichment analysis indicated the functional relevance of CRCAL-3 and CRCAL-4 in association with cell cycle. Our data highlight the capability of RNA-seq to discover novel lncRNAs involved in human carcinogenesis, which may serve as alternative biomarkers and/or molecular treatment targets. Overall design: 6 total samples consisting of 3 matched pairs of colorectal cancer (CRC) and matched normal mucosa (NM)
Publication Title
A RNA-Sequencing approach for the identification of novel long non-coding RNA biomarkers in colorectal cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 172 Downloadable Samples
Description
Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. Overall design: A population of 25 transfected TF1 cells were expanded and forwarded to a combination of 1) ATAC-seq and single cell RNA-seq. The single-cell RNA-seq data are listed here. Meta data includes heteroplasmic variant information per cell as well as the group assigned based on the lentiviral barcoding
Publication Title
Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 135 Downloadable Samples
Description
Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. A variety of experimental designs using cells derived from both in vitro and in vivo to determine the efficacy of using mtDNA mutations in human clonal tracing. Overall design: A population of 30 primary hematopoietic cells were expanded and forwarded to a combination of ATAC-seq and single cell RNA-seq. single cell RNA-seq samples are listed here.
Publication Title
Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 81 Downloadable Samples
- NextSeq 500
Description
Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. A variety of experimental designs using cells derived from both in vitro and in vivo to determine the efficacy of using mtDNA mutations in human clonal tracing. Overall design: Individually sorted cells from clonally derived TF1 clones (C9, D6, and G10) were processed with single cell RNA-seq (Smart-seq2)
Publication Title
Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- NextSeq 500
Description
Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. A variety of experimental designs using cells derived from both in vitro and in vivo to determine the efficacy of using mtDNA mutations in human clonal tracing. Overall design: Cells from 3 separate TF1 clones (C9, D6, and G10) were processed with bulk RNA-seq (Smart-seq2)
Publication Title
Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
We report the first RNA-Seq experiments profiling the effects of DEK loss in HNSCC. Our data also incorporates HPV+ and HPV- tumors to idenfity HPV-dependent and -independent gene signatures. Overall design: RNA-Seq of DEK-dependent gene signatures in HNSCC cell lines
Publication Title
IRAK1 is a novel DEK transcriptional target and is essential for head and neck cancer cell survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Chromosome 5q deletions (del(5q)) are common in high-risk (HR) Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML); however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q) HR-MDS/AML and miR-146a-/- hematopoietic stem/progenitor cells (HSPC) results in TRAF6/NF- activation. Increased survival and proliferation of HSPC from miR-146alow HR-MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62), expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-B-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-B signaling, as disrupting the p62-TRAF6 signaling complex results in cell cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q) HR-MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-B to sustain TRAF6/NF-B signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
Publication Title
Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-κB gene network.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bortezomib (Velcade) is widely used for the treatment of various human cancers, however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that Bortezomib induces proteasome-independent degradation of TRAF6 protein, but not mRNA, in Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) cell lines and primary cells. The reduction in TRAF6 protein coincides with Bortezomib-induced autophagy, and subsequently with apoptosis in MDS/AML cells. RNAi-mediated knockdown of TRAF6 sensitized Bortezomib-sensitive and -resistant cell lines, underscoring the importance of TRAF6 in Bortezomib-induced cytotoxicity. Bortezomib-resistant cells expressing an shRNA targeting TRAF6 were resensitized to the cytotoxic effects of Bortezomib due to down-regulation of the proteasomal subunit alpha-1 (PSMA1). To uncover the molecular consequences following loss of TRAF6 in MDS/AML cells, we applied gene expression profiling and identified an apoptosis gene signature. Knockdown of TRAF6 in MDS/AML cell lines or patient samples resulted in rapid apoptosis and impaired malignant hematopoietic stem/progenitor function. In summary, we describe novel mechanisms by which TRAF6 is regulated through Bortezomib/autophagy-mediated degradation and by which it alters MDS/AML sensitivity to Bortezomib by controlling PSMA1 expression.
Publication Title
Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1.
Sample Metadata Fields
Treatment
View Samples