We used a whole genome approach to identify major functional gene categories (including xenobiotic transporters and metabolizing enzymes) whose expression depends on gestational age. STUDY DESIGN: We compared gene expression profiles of 1st (45-59 days) and 2nd trimester (109-115 days), and C-section term placentae. RESULTS: In 1st trimester placentae, genes related to cell cycle, DNA, aminoacids and carbohydrate metabolism were significantly overrepresented, while genes related to signal transduction were downregulated. In the organism defense category, we identified genes involved in chemical response, metabolism, and transport. Analysis of signal transduction pathways suggested, and subsequently confirmed independently, that the Wnt pathway was regulated by gestational age. CONCLUSIONS: Our study will serve as a reference database to gain insight into the regulation of gene expression in the developing placentae and, thus, allow comparisons with placentae from complicated pregnancies such as those in women experiencing gestational diabetes, pre-eclampsia and teratogenic sequelae.
Profiling gene expression in human placentae of different gestational ages: an OPRU Network and UW SCOR Study.
No sample metadata fields
View SamplesPrimary RNAseq data for 103 highly purified immunocyte populations representing all lineages and several differentiation cascades, profiled using the ImmGen ULI pipeline. Overall design: These RNAseq profiles were generated by ImmGen labs in a combined study associating RNAseq and ATACseq performed on cell populations sorted in parallel (companion ATACseq datasets are found in GSE100738). The 103 cell populations include all adaptive and innate lymphocytes (B, abT, gdT, Innate-Like Lymphocytes), myeloid cells (dendritic cells, macrophages, monocytes), mast cells and neutrophils. Most were prepared from baseline unchallenged mice, some after cell activation (LPS, anti-CD3, viral infection). For B and T lymphocytes, many successive steps of their known differentiation cascades in the thymus and bone marrow are included. ---------------------------------------- Immunological Genome Project Consortium
The cis-Regulatory Atlas of the Mouse Immune System.
Age, Specimen part, Cell line, Subject
View SamplesExon usage analysis in in vitro cultured fibroblast cells. To assay the genome-wide splicing changes during cellular senescence, we performed splicing analysis on young and old normal fibroblasts, and in fibroblasts +/- tert (telomerase protein subunit Tert immortalized).
Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts.
Specimen part, Disease, Disease stage, Subject
View SamplesCanonical Wnt signalling regulates the self-renewal of most if not all stem cell systems. In the blood system, the role of Wnt signalling has been subject of much debate, with positive and negative roles of Wnt signalling proposed for hematopoietic stem cells (HSC). As we have shown previously, this controversy can be largely explained by the effects of different dosages of Wnt signalling. What remained unclear however, was why high Wnt signals would lead to loss of reconstituting capacity. To better understand this phenomenon, we have taken advantage of a series of hypomorphic mutant Apc alleles resulting in a broad range of Wnt dosages in HSCs, purified those HSCs and performed whole genome gene expression analyses. Gene expression profiling and functional studies show that HSCs with APC mutations lead to high Wnt levels , enhanced differentiation and diminished proliferation, but have no effect on apoptosis, collectively leading to loss of stemness. Thus, we provide mechanistic insight into the role of APC mutations and Wnt signalling in HSC biology. As Wnt signals are explored in various in vivo and ex vivo expansion protocols for HSCs, our findings also have clinical ramifications.
High Levels of Canonical Wnt Signaling Lead to Loss of Stemness and Increased Differentiation in Hematopoietic Stem Cells.
No sample metadata fields
View SamplesAdipose stroma in the mouse mammary gland undergoes remodeling throughout the 5 stages of development. These include nulliparous (virgin;never been pregnant), pregnant, lactating, involuting and regressed.
Pregnancy-associated breast cancers are driven by differences in adipose stromal cells present during lactation.
Specimen part
View SamplesThe goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling of exosomal RNA isolated from breast cancer patients before, during and after radiation therapy.
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Subject
View SamplesThe goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling for exosomal RNA isolated from stroma cell (MRC5) or stroma/breast cancer cell co-culture (MRC5 and 1833).
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Cell line, Subject
View SamplesNetworks of coordinated alternative splicing (AS) events play critical roles in development and disease. However, a comprehensive knowledge of the factors that regulate these networks is lacking. We describe a high-throughput system for systematically linking trans-acting factors to endogenous RNA regulation events. Using this system, we identify hundreds of factors associated with diverse regulatory layers that positively or negatively control AS events linked to cell fate. Remarkably, more than one third of the new regulators are transcription factors. Further analyses of the zinc finger protein Zfp871 and BTB/POZ domain transcription factor Nacc1, which regulate neural and stem cell AS programs, respectively, reveal roles in controlling the expression of specific splicing regulators. Surprisingly, these proteins also appear to regulate target AS programs via binding RNA. Our results thus uncover a large ‘missing cache’ of splicing regulators among annotated transcription factors, some of which dually regulate AS through direct and indirect mechanisms. Overall design: RNA-Seq of N2A cells upon RNAi-mediated knockdown of Mbnl1/Mbnl2 or Nacc1, or control knockdown (1 replicate each), as well as upon knockdown of Srrm4 or Zfp871, or control knockdown (2 replicates each) vast-tools.AltSplicing_Mbnl.Nacc1.tab: Primary vast-tools output for Mbnl and Nacc1 knockdowns vast-tools.AltSplicing_Srrm4.Zfp871.tab: Primary vast-tools output for Srrm4 and Zfp871 knockdowns AltSplicing_Mbnl.Nacc1.tab: Filtered PSI values and differential AS annotation for Mbnl and Nacc1 knockdowns AltSplicing_Srrm4.Zfp871.tab: Filtered PSI values and differential AS annotation for Srrm4 and Zfp871 knockdowns Expression_Mbnl.Nacc1.tab: Raw and read counts per gene, normalized expression and fold-change for Mbnl and Nacc1 knockdowns Expression_Srrm4.Zfp871.tab: Raw read counts per gene, normalized expression and fold-change (edgeR analysis) for Srrm4 and Zfp871 knockdowns
Multilayered Control of Alternative Splicing Regulatory Networks by Transcription Factors.
Cell line, Subject
View SamplesUnrestrained receptor tyrosine kinase (RTK) signaling and epigenetic deregulation are root causes of tumorigenesis. We establish linkage between these processes by demonstrating that aberrant RTK signaling unleashed by oncogenic HRasG12V or loss of negative feedback through Sprouty gene deletion remodels histone modifications associated with active typical and super-enhancers. However, while both lesions disrupt the Ras-Erk axis, the expression programs, enhancer signatures, and transcription factor networks modulated upon HRasG12V-transformation or Sprouty deletion are largely distinct. Oncogenic HRasG12V elevates histone 3 lysine 27 acetylation (H3K27ac) levels at enhancers near the transcription factor Gata4 and the kinase Prkcb, as well as their expression levels. We show that Gata4 is necessary for the aberrant gene expression and H3K27ac marking at enhancers, and Prkcb is required for the oncogenic effects of HRasG12V-driven cells. Taken together, our findings demonstrate that dynamic reprogramming of the cellular enhancer landscape is a major effect of oncogenic RTK signaling. Overall design: We assessed gene expression changes upon loss of feedback regulation through Sprouty (Spry) deletion, and upon unrestrained signaling driven by mutant oncogenes. RNA-seq was performed in biological triplicate; replicate number is included in the sample name. Spry124fl/fl (VEC) and Spry124-/- (CRE) MEFs were profiled in three conditions: unsynchronized (U), serum starved (S), and serum starved and FGF treated (F). Spry124fl/fl (VEC) MEFs transduced with empty vector (EV) control or the indicated oncogenes (KRasG12V, HRasG12V, and BRafV600E) as well as Spry124-/- (CRE) MEFs transduced with EV control were profiled in the unsynchronized state.
Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape.
No sample metadata fields
View SamplesWe profiled gene expression in livers depleted of NCOR (nuclear receptor corepressor) along with wild-type livers as control.
Deacetylase-independent function of HDAC3 in transcription and metabolism requires nuclear receptor corepressor.
No sample metadata fields
View Samples