The objective of this study was to understand the gene expression changes during granulosa cell tumor development in Smad1/5/8 mutant ovaries.
Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice.
No sample metadata fields
View SamplesSchwann cell maturation is tightly controlled by a set of transcriptional regulators. We have deleted the zinc-finger transcription factor Sip1 specifically from immature Schwann cells and observed a dramatic developmental delay.
Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair.
Age, Specimen part
View SamplesWe performed gene expression pofiling of Zeb2cKO and control sciatic nerves and identified significantly changed genes ZEB2 is also known as SIP1 Overall design: 4 RNA-Seq samples from P7 sciatic nerves of Ctrl and Zeb2 cKO mice (duplicatess, Ctrl and cKO)
Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system.
Specimen part
View SamplesMyelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and -catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair.
Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system.
Specimen part
View SamplesZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in EMT-dependent tumor metastasis. While the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is upregulated by activated T cells, specifically in the KLRG1hi effector CD8+ T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8+ T cells following primary and secondary infection with a severe impairment in the generation of the KLRG1hi effector-memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress CD127 and IL-2 in CD8+ T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box-sites in the ZEB2 gene and that T-bet and ZEB2 regulate similar gene-expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Taken together, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8+ T cells.
Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection.
Sex, Age, Specimen part
View SamplesTo capture the Zeb2-dependent transcriptional changes in early cell state/fate decisions we performed RNA-seq on Zeb2 control and Zeb2 knockout cells. We chose three stages, which correspond in control ESCs to the naive pluripotent state (d0; very low amounts of Zeb2 mRNA), multipotent progenitors (d4, low Zeb2 mRNA/protein) and early neural progenitors (d6, high Zeb2 mRNA/protein), respectively. Overall design: Three biological replicates of Zeb2 control (Ctrl) and Zeb2 knockout (KO) samples on day 0, day 4 and day 6 of neural differentiation were used in this study (18 samples in total)
Zeb2 Regulates Cell Fate at the Exit from Epiblast State in Mouse Embryonic Stem Cells.
Cell line, Subject
View SamplesIn this study we determine the transcriptional profile by RNAseq of mESC in the absence of Smad1 and Smad5 and in subpopulation of mESC with different levels of BMP-SMAD activation. Overall design: Transcriptome analysis using RNAseq was performed on 3 biological replicates of BRE negative and positive mESC subpopulations, which were collected in pairs at 3 different times. Transcriptome analysis using RNAseq was performed on Smad1/5 floxed (FL) and knockout (KO) mESC. Two different parental cell lines were used. For each parental cell line we analyzed one Smad1/5 FL sample and two Smad1/5 KO samples, resulting in respectively two and four biological replicates for the FL and KO conditions.
BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells.
No sample metadata fields
View SamplesWe sequenced mRNA from 6 samples of FACsorted telencephalons from E14.5 Sip1|Nkx2-1 knockout and WT|Nkx2-1 control mouse embryos to find differentially expressed genes in the absence of the transcription factor Sip1. Overall design: Examination of mRNA levels in 3 control and 3 Sip1|Nkx2-1 knockout samples
Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.
Specimen part, Cell line, Subject
View SamplesWe used RNA-seq to investigate gene expression variation in Malpighian tubules, which have a function analogous to that of human kidneys. In order to characterize population differentiation, we sequenced the Malpighian tubule transcriptomes of flies derived from two populations, one from sub-Saharan Africa (Zimbabwe) and one from Europe (the Netherlands). Males and females were examined separately. Overall, we found a high amount of differential expression between sexes (2,308 genes) and populations (2,474 genes). Although most of the differentially expressed genes were consistent between sexes and populations, there were 615 genes showed sex-biased expression in only one population and 557 genes showed population-biased expression in only one sex. Overall design: mRNA expression profiles of Drosophila melanogaster Malpighian tubules from adult males and females from a European and an African population (2 biological replicates per sex and population)
Population- and sex-biased gene expression in the excretion organs of Drosophila melanogaster.
Sex, Subject
View Samples