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SRP049340
Homo sapiens
166 Downloadable Samples
IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. Overall design: mRNA sequencing of primary and secondary fibroblasts with reference BJ (supplementary file fibroblasts), reprogramming intermendiates from untreated hiF-T reprogramming (supplementary file reprogramming), or selective time points upon LSD1 inhibitor treatment (supplementary file LSD1i). RNA samples used for mRNA sequencing are the same used for smallRNA sequencing.
Publication Title
Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 52 Downloadable Samples
- IlluminaHiSeq2500
Description
Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. Overall design: single cell RNA-seq profiles from 52 unfractionated hiF-T cells after 10 days of reprogramming
Publication Title
Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 15 Downloadable Samples
Affymetrix Zebrafish Genome Array (zebrafish)
Description
Investigation of expression differences between skin and melanomas from a transgenic BRAFV600E zebrafish model of melanoma
Publication Title
DHODH modulates transcriptional elongation in the neural crest and melanoma.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Investigation of expression differences between melanomas harvested from MiniCoopR-GFP versus MiniCoopR-SETDB1 transgenic zebrafish
Publication Title
DHODH modulates transcriptional elongation in the neural crest and melanoma.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Identification of genes differentially regulated after treatment of zebrafish embryos from 50% epiboly to 24hpf with 6.5uM leflunomide
Publication Title
DHODH modulates transcriptional elongation in the neural crest and melanoma.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
Abstract Background. The cellular effects of androgen are transduced through the androgen receptor, which controls the expression of genes that regulate biosynthetic processes, cell growth, and metabolism. Androgen signaling also impacts DNA damage signaling through mechanisms involving gene expression and transcription-associated DNA damaging events. Defining the contributions of androgen signaling to DNA repair is important for understanding androgen receptor function, and it also has important translational implications. Methods. We generated RNA-seq data from multiple prostate cancer lines and used bioinformatic analyses to characterize androgen-regulated gene expression. We compared the results from cell lines with gene expression data from prostate cancer xenografts, and patient samples, to query how androgen signaling and prostate cancer progression influences the expression of DNA repair genes. We performed whole genome sequencing to help characterize the status of the DNA repair machinery in widely used prostate cancer lines. Finally, we tested a DNA repair enzyme inhibitor for effects on androgen-dependent transcription. Results. Our data indicates that androgen signaling regulates a subset of DNA repair genes that are largely specific to the respective model system and disease state. We identified deleterious mutations in the DNA repair genes RAD50 and CHEK2. We found that inhibition of the DNA repair enzyme MRE11 with the small molecule mirin inhibits androgen-dependent transcription and growth of prostate cancer cells. Conclusions. Our data supports the view that crosstalk between androgen signaling and DNA repair occurs at multiple levels, and that DNA repair enzymes in addition to PARPs, could be actionable targets in prostate cancer. Overall design: RNA was extracted from PC3-AR, VCaP, and LNCaP cells under untreated and androgen (2 nM, R1881) treated conditions. A total of 21 samples were sequenced with 3 replicates for each condition.
Publication Title
Genomic analysis of DNA repair genes and androgen signaling in prostate cancer.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recently, we identified a population of Oct4+Sca-1+Lin-CD45- very small embryonic-like stem-cells (VSELs) in adult tissues. Open chromatin structure of pluripotency genes and genomic imprinting-related epigenetic mechanisms maintain pluripotency and quiescence of VSELs, respectively. However, global transcriptome signature of this rare stem-cell population remains elusive. Here, we demonstrate by genomewide gene-expression analysis with a small number of highly purified murine bone-marrow (BM)-derived VSELs, that Oct4+ VSELs i) express a similar, yet nonidentical, transcriptome as embryonic stem-cells (ESCs), ii) up-regulate cell-cycle checkpoint genes, iii) down-regulate genes involved in protein turnover and mitogenic pathways, and iv) highly express Ezh2, a polycomb group protein.
Publication Title
Global gene expression analysis of very small embryonic-like stem cells reveals that the Ezh2-dependent bivalent domain mechanism contributes to their pluripotent state.
Sample Metadata Fields
Age, Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Under conditions of hormonal adjuvant treatment the estrogen receptor apoprotein supports breast cancer cell cycling through the retinoic acid receptor 1 apoprotein.
Publication Title
During hormone depletion or tamoxifen treatment of breast cancer cells the estrogen receptor apoprotein supports cell cycling through the retinoic acid receptor α1 apoprotein.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Ewing Sarcoma is caused by a pathognomonic genomic translocation that places an N-terminal EWSR1 gene in approximation with one of several ETS genes (typically FLI1). This aberration, in turn, alters the transcriptional regulation of more than five hundred genes and perturbs a number of critical pathways that promote oncogenesis, cell growth, invasion, and metastasis. Among them, translocation-mediated up-regulation of the insulin-like growth factor receptor 1 (IGF-1R) and mammalian target of rapamycin (mTOR) are of particular importance since they work in concert to facilitate IGF-1R expression and ligand-induced activation, respectively, of proven importance in ES transformation. When used as a single agent in Ewing sarcoma therapy, IGF-1R or mTOR inhibition leads to rapid counter-regulatory effects that blunt the intended therapeutic purpose. Therefore, identify new mechanisms of resistance that are used by Ewing sarcoma to evade cell death to single-agent IGF-1R or mTOR inhibition might suggest a number of therapeutic combinations that could improve their clinical activity.
Publication Title
IGF-1R and mTOR Blockade: Novel Resistance Mechanisms and Synergistic Drug Combinations for Ewing Sarcoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
We were interesed in defining the gene signautre of volar skin.
Publication Title
To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease.
Sample Metadata Fields
No sample metadata fields
View Samples