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accession-icon SRP091764
Modeling signaling-dependent pluripotent cell states with boolean logic can predict cell fate transitions [II]
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Pluripotent stem cells (PSCs) exist in multiple stable states, each with specific cellular properties and molecular signatures. The process by which pluripotency is either maintained or destabilized to initiate specific developmental programs is poorly understood. We have developed a model to predict stabilized PSC gene regulatory network (GRN) states in response to combinations of input signals. While previous attempts to model PSC fate have been limited to static cell compositions, our approach enables simulations of dynamic heterogeneity by combining an Asynchronous Boolean Simulation (ABS) strategy with simulated single cell fate transitions using a Strongly Connected Components (SCCs). This computational framework was applied to a reverse-engineered and curated core GRN for mouse embryonic stem cells (mESCs) to simulate responses to LIF, Wnt/ß-catenin, FGF/ERK, BMP4, and Activin A/Nodal pathway activation. For these input signals, our simulations exhibit strong predictive power for gene expression patterns, cell population composition, and nodes controlling cell fate transitions. The model predictions extend into early PSC differentiation, demonstrating, for example, that a Cdx2-high/Oct4-low state can be efficiently generated from mESCs residing in a naïve and signal-receptive state sustained by combinations of signaling activators and inhibitors. Overall design: Examination of perturbed PSCs versus control PSCs and mesoderm progenitors Mouse pluripotent stem cells were grown on tissue culture plates for two days in serum-containing, feeder free medium supplemented with the following cytokines/small molecules: 2i = CHIR99021 (Reagents Direct 27-H76 – 3µM) & PD0325901 (Reagents Direct 39-C68 – 1µM) Jaki = JAK inhibitor (EMD Millipore 420097 – 2.0µM) BMP = BMP4 (R&D Systems 314-BP-010 – 10ng/ml) Alk5i = ALK5 inhibitor II (Cedarlane ALX-270-445 - 10µM)

Publication Title

Modeling signaling-dependent pluripotency with Boolean logic to predict cell fate transitions.

Sample Metadata Fields

Cell line, Treatment, Subject, Time

View Samples
accession-icon SRP079965
Sequential loss of plasticity during trophectoderm and inner cell mass lineage segregation in the mouse embryo
  • organism-icon Mus musculus
  • sample-icon 292 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

We report the whole transcriptome data of single-cells derived from the early 16-cell stage to the 64-cell stage in the mouse embryo. Overall design: RNA from 262 cells from 36 mouse embryos (16- to 64-cell stage)

Publication Title

Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE28711
Polycomb function during oogenesis is required for mouse early embryonic development
  • organism-icon Mus musculus
  • sample-icon 23 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Polycomb function during oogenesis is required for mouse embryonic development.

Sample Metadata Fields

Specimen part, Treatment

View Samples
accession-icon GSE23033
Polycomb function during oogenesis is required for mouse early embryonic development (germinal vesicle oocytes)
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

In mammals, totipotent pre-implantation embryos are formed by fusion of highly differentiated oocytes and spermatozoa. Acquisition of totipotency concurs with remodeling of chromatin states of parental genomes (epigenetic reprogramming), changes in maternally contributed transcriptome and proteome, and zygotic genome activation. Genomes of mature germ cells are more proficient in supporting embryonic development than those of somatic cells. It is currently unknown whether transgenerational inheritance of chromatin states present in mature gametes underlies the efficacy of early embryonic development after natural conception. Here, we show that Ring1 and Rnf2, two core components of the Polycomb Repressive Complex 1 (PRC1), serve redundant gene regulatory functions during oogenesis that are required to support embryonic development beyond the two-cell stage. Numerous developmental regulatory genes that are established Polycomb targets in various somatic cell types are de-repressed in Ring1/Rnf2 double mutant (dm) fully grown germinal vesicle (GV) oocytes. Translation of tested aberrant maternal transcripts is, however, delayed until after fertilization. Exchange of maternal pro-nuclei between control and Ring1/Rnf2 maternally dm early zygotes demonstrates an essential role for Ring1 and Rnf2 during oogenesis in defining cytoplasmic and nuclear maternal contributions that are both essential for proper initiation of embryonic development. A large number of genes up-regulated in Ring1/Rnf2 dm GV oocytes harbor PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) in spermatozoa and in embryonic stem cells (ESCs), and are repressed during normal oogenesis and early embryogenesis. These data strongly support the model that Polycomb acts in the female and male germline to silence differentiation inducing genes and to program chromatin states, thereby sustaining developmental potential across generations.

Publication Title

Polycomb function during oogenesis is required for mouse embryonic development.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE28710
Polycomb function during oogenesis is required for mouse early embryonic development (2-cell embryos)
  • organism-icon Mus musculus
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

In mammals, totipotent pre-implantation embryos are formed by fusion of highly differentiated oocytes and spermatozoa. Acquisition of totipotency concurs with remodeling of chromatin states of parental genomes (epigenetic reprogramming), changes in maternally contributed transcriptome and proteome, and zygotic genome activation. Genomes of mature germ cells are more proficient in supporting embryonic development than those of somatic cells. It is currently unknown whether transgenerational inheritance of chromatin states present in mature gametes underlies the efficacy of early embryonic development after natural conception. Here, we show that Ring1 and Rnf2, two core components of the Polycomb Repressive Complex 1 (PRC1), serve redundant gene regulatory functions during oogenesis that are required to support embryonic development beyond the two-cell stage. Numerous developmental regulatory genes that are established Polycomb targets in various somatic cell types are de-repressed in Ring1/Rnf2 double mutant (dm) fully grown germinal vesicle (GV) oocytes. Translation of tested aberrant maternal transcripts is, however, delayed until after fertilization. Exchange of maternal pro-nuclei between control and Ring1/Rnf2 maternally dm early zygotes demonstrates an essential role for Ring1 and Rnf2 during oogenesis in defining cytoplasmic and nuclear maternal contributions that are both essential for proper initiation of embryonic development. A large number of genes up-regulated in Ring1/Rnf2 dm GV oocytes harbor PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) in spermatozoa and in embryonic stem cells (ESCs), and are repressed during normal oogenesis and early embryogenesis. These data strongly support the model that Polycomb acts in the female and male germline to silence differentiation inducing genes and to program chromatin states, thereby sustaining developmental potential across generations.

Publication Title

Polycomb function during oogenesis is required for mouse embryonic development.

Sample Metadata Fields

Treatment

View Samples
accession-icon GSE26725
Gene expression analysis of 12 B-cell Chronic Lymphocytic Leukemia samples and 5 CD19+ control samples
  • organism-icon Homo sapiens
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In this study, we present evidence that MYB (v-myb myeloblastosis viral oncogene homolog) is overexpressed in a subset of B-CLL patients. MYB physically associates with the promoter of MIR155 host gene (MIR155HG, also known as BIC, B-cell integration cluster) and stimulates its transcription. This coincides with the hypermethylated histone H3K4 residue and spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide evidence of oncogenic activities of MYB in B-CLL that include its stimulatory role in MIR155HG transcription.

Publication Title

MYB transcriptionally regulates the miR-155 host gene in chronic lymphocytic leukemia.

Sample Metadata Fields

Specimen part, Disease, Disease stage

View Samples
accession-icon GSE2359
Sorted wing disc proneural cluster cells
  • organism-icon Drosophila melanogaster
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome Array (drosgenome1)

Description

Fluorescence-activated cell sorting of M4-GFP wing imaginal disc cells was used to recover a purified population of the cells that comprise the proneural clusters from which sensory organ precursors of the peripheral nervous system (PNS) arise. Whole-genome microarray analysis and in situ hybridization was then used to identify and verify a set of genes that are preferentially expressed in proneural cluster cells. Genes in this set encode proteins with a diverse array of implied functions, and loss-of-function analysis of two candidate genes shows that they are indeed required for normal PNS development.

Publication Title

Genetic programs activated by proneural proteins in the developing Drosophila PNS.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE13436
Influence of hyperthyroid conditions on gene expression in rat
  • organism-icon Rattus norvegicus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE21641
Dose-dependent gene expression analysis of cardiomyocytes treated with DEHP (1-50 ug/mL)
  • organism-icon Rattus norvegicus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Gene 1.0 ST Array (ragene10st)

Description

We used microarrays to expression profile cardiomyocytes from neonatal Sprague-Dawley rats treated with 1 to 50 ug/mL DEHP and control (0.1% DMSO) to identify changes in gene expression related to connexin-43 expression, calcium handling, arrhythmogenesis and mechanical motion.

Publication Title

Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity.

Sample Metadata Fields

Age, Specimen part, Treatment

View Samples
accession-icon GSE21640
Gene expression analysis of cardiomyocytes treated with a clinically relevant concentration of DEHP (50 ug/mL)
  • organism-icon Rattus norvegicus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Gene 1.0 ST Array (ragene10st)

Description

We used microarrays to expression profile cardiomyocytes from neonatal Sprague-Dawley rats treated with 50 ug/mL DEHP and control (0.1% DMSO) to identify changes in gene expression related to connexin-43 expression, calcium handling, arrhythmogenesis and mechanical motion.

Publication Title

Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity.

Sample Metadata Fields

Age, Specimen part, Treatment

View Samples
...

refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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