Project description:CTCF ChIP-seq of 39 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011059 (dataset).
Project description:H3K27ac ChIP-seq of 79 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). In addition, 4 samples derived from CD34+ cord blood cells of healthy donors were included. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011060 (dataset).
Project description:Embryonic genome activation (EGA) marks the onset of embryonic program and enables the transition toward the first lineage specification. However, the molecular features of EGA and the transcription factors (TFs) orchestrating this process remain unclear. Here, by performing single-cell RNA-seq on bovine embryos, we reveal that major EGA is asynchronously initiated among blastomeres at the 8-cell stage. Integrative analyses reveal distinctive protein accumulation compared to transcription and translation activation during bovine EGA. Furthermore, we investigate the role of SP1, a TF activated at the minor EGA stage, with motifs enriched in accessible chromatin during major EGA stage in bovine and human embryos. SP1 deficiency leads to morula arrest in bovine and impairs EGA in human embryos. Multi-omics analysis demonstrates that SP1 promotes early lineage gene expression by modulating nearby chromatin states in bovine and directly targets key EGA genes in human embryos. Together, our study delineates the dynamics of bovine EGA and uncovers the conserved and species-specific roles of SP1 in regulating EGA and early development in mammals.
Project description:Embryonic genome activation (EGA), a pivotal transcriptional event during preimplantation development, is accompanied by post-transcriptional regulation of maternal mRNAs. Disentangling the transcriptional output of the newly activated embryonic genome from concomitant post-transcriptional processing is important for decoding EGA dynamics.Here, using optimized low-input SLAM-seq (thiol(SH)-linked alkylation for the metabolic sequencing) in mouse embryos, we delineates the temporal hierarchy of EGA nascent transcription during mouse preimplantation embryogenesis and uncovers a mechanistic link between EGA and the first lineage specification, providing new insights into the regulatory architecture of early mammalian development.
Project description:<p>This is a multi-centre, case-controlled study to develop a dataset containing 1000 MS cases and 1000 matched controls and to associate DNA sequence (allelic) variations with MS phenotypes.</p> <p>Study subjects were enrolled through a prospective effort initiated in 2003. Three MS clinical centres were involved in subject recruitment and biological specimen collection using identical inclusion/exclusion criteria, two in Europe (Vrije Universiteit Medical Center, Amsterdam; and University Hospital Basel) and one in the US (University of California San Francisco). This study recruited subjects of northern-European ancestry with a diagnosis of MS (<a href="http://www.ncbi.nlm.nih.gov/pubmed/11456302" target="_blank">McDonald et al., 2001</a>), with dissemination in time and space. Patients with Clinically Isolated Syndromes (CIS) were also included if they fulfilled 3 of the 4 Barkhof criteria for dissemination in space as per application of the McDonald criteria (<a href="http://www.ncbi.nlm.nih.gov/pubmed/11456302" target="_blank">McDonald et al., 2001</a>). While recruitment predominantly included subjects with a relapsing onset of MS, individuals with all clinical subtypes of the disease participated, including clinically isolated syndrome (CIS), relapsing remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive relapsing MS (PRMS).</p> <p>The control group consisted of unrelated individuals, primarily spouses/partners, friends, and other volunteers. Control subjects were of northern-European ancestry and matched as a group, proportionally with cases according to age (±5 years) and gender. A familial history or current diagnosis of MS as well as a relation to another case or control subject were considered exclusionary for this group.</p> <p>Protocols were approved by the Committees on Human Research at all Institutions and informed consent was obtained from all participants prior to participation in the study.</p> <p><b>Primary Study Objective:</b><br/>To identify DNA sequence variations (genotype) and flanking sequences that are associated with clinical factors (phenotype) which differ between study subjects with and without MS.</p> <p><b>Secondary Study Objectives:</b> <ol> <li>To develop a clinical dataset including quantitative measures of 1000 well-characterized cases with MS, and 1000 ethnically matched controls.</li> <li>To identify other genotype-phenotype associations in MS study subjects such as magnetic resonance imaging (MRI) measures of disease burden and/or severity.</li> <li>To identify or confirm candidate surrogate markers of neurodegeneration using a variety of techniques including biochemical assays, blood transcriptome analysis, plasma proteomics and MRI*.</li> </ol> </p> <p><b><u>Genotyping</u></b><br/>Genotyping of the complete dataset was performed at the Illumina facilities using the Sentrix® HumanHap550 BeadChip.</p> <p><small><i>*MRI results are not available on dbGaP.</i></small></p>
Project description:RNA was isolated from purified human CD8 cells that were incubated with anti-HER2/CD3 TDB in the presence of SK-BR-3 cells. This dataset only contains the metadata and processed data. Raw data can be accessed via the EGA accession EGAS00001003734
Project description:Single-cell RNA-seq libraries were generated from human PBMCs that were incubated with anti-HER2/CD3 TDB in the presence of KPL-4 cells. This dataset only contains the metadata and processed data. Raw data can be accessed via the EGA accession EGAS00001003734
Project description:Hi-C of 17 primary samples obtained from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). As healthy controls, Hi-C of CD34+ HSPCs from 3 healthy donors were used. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011051 (dataset).