This SuperSeries is composed of the SubSeries listed below.
Targeted expression profiling by RNA-Seq improves detection of cellular dynamics during pregnancy and identifies a role for T cells in term parturition.
Subject
View SamplesMaternal plasama colected longitudinally were profiled using paired-end Illumina RNA-Seq with globin reduction to evaluate changes with gestational age and with labor in normal pregnancy. Overall design: The study included normal pregnancies with (n=8) and without (n=8) spontaneous labor at term. Half of the women in each group had 3 longitudinal samples taken from 12.1-40.3 weeks of gestation, while the other half of women had only one sample taken at term before delivery, for a total of 32 samples.
Targeted expression profiling by RNA-Seq improves detection of cellular dynamics during pregnancy and identifies a role for T cells in term parturition.
Subject
View SamplesMaternal plasama colected longitudinally were profiled using Affymetrix Human Transcriptome Arrays to evaluate changes with gestational age and with labor in normal pregnancy.
Targeted expression profiling by RNA-Seq improves detection of cellular dynamics during pregnancy and identifies a role for T cells in term parturition.
Subject
View SamplesThe role of mitochondria dynamics and its molecular regulators remains largely unknown during naïve-to-primed pluripotent cell interconversion. Here we report that mitochondrial MTCH2 is a regulator of mitochondrial fusion, essential for the naïve-to-primed interconversion of murine embryonic stem cells (ESCs). During this interconversion, wild-type ESCs elongate their mitochondria and slightly alter their glutamine utilization. In contrast, MTCH2-/- ESCs fail to elongate their mitochondria and to alter their metabolism, maintaining high levels of histone acetylation and expression of naïve pluripotency markers. Importantly, enforced mitochondria elongation by the pro-fusion protein Mitofusin (MFN) 2 or by a dominant negative form of the pro-fission protein dynamin-related protein (DRP) 1 is sufficient to drive the exit from naïve pluripotency of both MTCH2-/- and wild-type ESCs. Taken together, our data indicate that mitochondria elongation, governed by MTCH2, plays a critical role and constitutes an early driving force in the naïve-to-primed pluripotency interconversion of murine ESCs. Overall design: Examination of WT and MTCH2 KO ESC and EpiLC mouse embryonic stem cells transcriptome
MTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells.
Specimen part, Subject
View SamplesHaving found that LexA degradation was significantly higher under apoptotic like death (ALD) than under SOS conditions, we hypothesized that additional genes tightly regulated by LexA would be transcribed under ALD conditions.
Apoptosis-like death, an extreme SOS response in Escherichia coli.
Disease, Treatment
View SamplesPlasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. While conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors (CLP). Here we found that pDCs developed predominantly from IL7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH+Ly6D+ precursors indicated that pDC development requires high expression of the transcription factor IRF8, while pDC identity relies on TCF4. RNA sequencing of IL7R+ lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed by single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen. Overall design: Bulk RNA Seq was performed from sort purified DN, SP and DP lymphoid progenitors and BM pDCs of 4 individual mice
Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells.
Specimen part, Cell line, Subject
View SamplesPlasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. While conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors (CLP). Here we found that pDCs developed predominantly from IL7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH+Ly6D+ precursors indicated that pDC development requires high expression of the transcription factor IRF8, while pDC identity relies on TCF4. RNA sequencing of IL7R+ lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed by single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen. Overall design: BM and splenic pDCs were sorted from 3 mice and 3000 cells/sample were used for single cell RNA Seq (10x genomics)
Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation.
Cell line, Treatment
View SamplesThe branched chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. By performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem cell (LSC) and non-LSC populations, we found the BCAA pathway enriched and BCAT1 overexpressed in LSCs. We show that BCAT1, which transfers -amino groups from BCAAs to -ketoglutarate (KG), is a critical regulator of intracellular KG homeostasis. Next to its role in the tricarboxylic acid (TCA) cycle KG is an essential co-factor for KG-dependent dioxygenases such as EGLN1 and the TET family of DNA demethylases. Knockdown of BCAT1 in leukaemia cells caused accumulation of KG leading to HIF1a protein degradation mediated by EGLN1. This resulted in a growth and survival defect and abrogated leukaemia-initiating potential. In contrast, overexpression (OE) of BCAT1 in leukaemia cells decreased intracellular KG levels and caused DNA hypermethylation via altered TET activity. BCAT1high AMLs displayed a DNA hypermethylation phenotype similar to cases carrying mutant isocitrate dehydrogenase (IDHmut), in which TET2 is inhibited by the oncometabolite 2-hydroxyglutarate. High levels of BCAT1 strongly correlate with shorter overall survival in IDHwtTET2wt, but not IDHmut or TET2mut AMLs. Gene sets characteristic for IDHmut AMLs were enriched in IDHwtTETwtBCAT1high patient samples. BCAT1high AMLs showed robust enrichment for LSC signatures and paired sample analysis revealed a significant increase of BCAT1 levels upon disease relapse. In summary, by limiting intracellular KG, BCAT1 links BCAA catabolism to HIF1a stability and regulation of the epigenomic landscape. Our results suggest the BCAA-BCAT1-KG pathway as a therapeutic target to compromise LSC function in IDHwtTET2wt AML patients.
BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation.
Treatment
View SamplesBrassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Age, Specimen part, Treatment
View Samples