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SRP095535
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
Mouse oocyte maturation, fertilization, and reprogramming occur in the absence of transcription and thus must be regulated post-transcriptionally. Surprisingly, a major form of post-transcriptional regulation, microRNA-based transcript destabilization and translational inhibition, is lost during this developmental window. Here we evaluate the conservation, timing, and mechanism behind the loss of microRNA activity in oocytes. In both mouse and frogs, microRNA function was active in growing oocytes, but then lost during oocyte maturation. RNA-sequencing of the maturing oocytes uncovered expression of an alternative isoform of Ago2 lacking domains critical for its function. Introduction of full-length Ago2 together with an exogenous microRNA destabilized microRNA luciferase reporters. However, endogenous targets were still largely unaffected. These findings suggest that while it is possible to re-activate some aspects of microRNA activity by introducing full length Ago2, there are additional mechanisms to protect endogenous transcripts from microRNA activity in oocytes. Overall design: Total RNA from mouse GV and MII oocytes, embryonic stem cells, epi cells
Publication Title
Expression of Alternative Ago2 Isoform Associated with Loss of microRNA-Driven Translational Repression in Mouse Oocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 4000
Description
During early development, pluripotent cells of the epiblast show extensive rewiring of enhancers with little associated change in gene expression. The mechanisms underlying and purpose of this rewiring are largely unknown. Here we identified a transcription factor, GRHL2, that is both necessary and sufficient to activate latent enhancers during the transition from naïve embryonic stem cells (ESC) to primed epiblast cells (EpiC). GRHL2 is necessary to maintain expression of its targets in EpiCs. However, these genes are already expressed at equivalent levels in ESCs, suggesting these genes switch enhancer usage during the transition. Identification of alternative enhancers driving these genes in ESCs uncovered an enrichment for the ESC-specific KLF transcription factors. While many KLF targets remain expressed in EpiCs, GRHL2 only regulates a specific subset promoting an epithelial program. These data suggest a model where a large naïve-specific transcriptional network is partitioned into smaller networks to uncouple their regulation in EpiCs, providing more flexibility in gene regulation during lineage specification. Overall design: RNA-seq in wildtype embryonic stem cells (ESCs) and wildtype epiblast-like cells (EpiLCs)
Publication Title
GRHL2-Dependent Enhancer Switching Maintains a Pluripotent Stem Cell Transcriptional Subnetwork after Exit from Naive Pluripotency.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods: We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results: The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions: Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.
Publication Title
Human Lacrimal Gland Gene Expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Affymetrix expression arrays were used to compare expression patterns upon knockdown of PARP-1, PARG, SIRT1, or macroH2A in comparison to Luciferase control.
Publication Title
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) are enzymes that modify target proteins in the nucleus by the addition and removal, respectively, of ADP-ribose polymers. Although a role for PARP-1 in gene regulation has been well established, the role of PARG is less clear. To investigate how PARP-1 and PARG coordinately regulate global patterns of gene expression, we used short hairpin RNAs (shRNAs) to stably knockdown PARP-1 or PARG in MCF-7 cells, followed by expression microarray analyses.
Publication Title
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In mammals, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) constitute a nuclear NAD+ salvage pathway, regulating cellular functions of the NAD+-dependent deacetylase SIRT1. However, little is known about the molecular mechanisms by which NAD+ biosynthesis controls gene transcription in the nucleus. In this study, we show that stable knockdown of NAMPT or NMNAT-1 in MCF-7 breast cancer cells significantly reduced total cellular NAD+ levels. Expression microarray analyses demonstrate that both enzymes have broad and overlapping functions in gene regulation. SIRT1 is a key mediator of NAMPT- and NMNAT-1-dependent gene regulation, and is found at promoters of many of the target genes. Furthermore, SIRT1 deacetylase activity at these promoters is regulated by NAMPT and NMNAT-1. Most significantly, NMNAT-1 interacts with SIRT1 and is recruited to target gene promoters by SIRT1. Our results reveal an unexpected mechanism for the direct control of SIRT1 deacetylase activity at target gene promoters by NMNAT-1. Interactions between NMNAT-1 and SIRT1 at gene promoters may provide a platform for integration of multiple signaling pathways that regulate transcription.
Publication Title
Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NMNAT1 is a nuclear enzyme in the mammalian NAD+ salvage pathway. Expression microarray analysis was used to study the effect of NMNAT1 knockdown on gene expression in MCF-7 breast cancer cells.
Publication Title
Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SIRT1 is a nuclear NAD+-dependent protein deacetylase. Expression microarray analysis was used to study the effect of SIRT1 knockdown on gene expression in MCF-7 breast cancer cells.
Publication Title
Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NAMPT is an enzyme in the mammalian NAD+ salvage pathway. Expression microarray analysis was used to study the effect of NAMPT knockdown on gene expression in MCF-7 breast cancer cells.
Publication Title
Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Triple negative breast cancer (TNBC) is an aggressive subtype that lack targeted clinical therapies. In addition, TNBC is heterogeneous and was recently further sub-classified into seven TNBC subtypes that displayed unique gene expression patterns.
Publication Title
Patient-derived xenografts of triple-negative breast cancer reproduce molecular features of patient tumors and respond to mTOR inhibition.
Sample Metadata Fields
Specimen part
View Samples