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GSE95038
Homo sapiens
5 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Adoptive T cell therapy (ACT) is a promising therapeutic approach for cancer patients. The use of allogeneic T cell grafts will improve its applicability and versatility provided that inherent allogeneic responses are controlled. T cell activation is finely regulated by multiple signaling molecules that are transcriptionally controlled by epigenetic mechanisms. Through extensive chemical probe screening, we found that inhibiting DOT1L, a histone H3-lysine 79 methyltransferase, alleviated allogeneic T cell responses.
Publication Title
DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Adoptive T cell therapy (ACT) is a promising therapeutic approach for cancer patients. The use of allogeneic T cell grafts will improve its applicability and versatility provided that inherent allogeneic responses are controlled. Through extensive chemical probe screening, we found that inhibiting DOT1L, a histone H3-lysine 79 methyltransferase, alleviated allogeneic T cell responses. DOT1L inhibition with SGC0946 selectively ameliorated low-avidity T cell responses but not high-avidity antitumor T cell responses mediated by the high-affinity T cell receptor or chimeric antigen receptor. The inhibition of DOT1L in T cells prevented the development of graft-versus-host disease while retaining potent antitumor activity in xenogeneic ACT models. These results suggest that DOT1L inhibition may enable the safe and effective use of allogeneic antitumor T cells by suppressing unwanted immunological reactions in ACT. Overall design: To investigate how DOT1L inhibition modulates the T cell activation signal, we compared gene expression profiles between SGC0946-treated or DMSO-treated (control) T cells by RNA-sequencing analysis. Human CD8+ T cells derived from three different healthy donors were cultured in the presence of SGC0946 or DMSO. Total RNA was collected from each sample and gene expression profiles were analyzed by RNA-sequencing using an Illumina HiSeq 2500 sequencer.
Publication Title
DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
How the parental genomes of the very specialized sperm and oocyte cells are remodelled upon fertilization to confer totipotency has remained a tantalizing open questions. Indeed, in the case of mammals, the parental genomes undergo dramatic reprogramming upon fertilization, including differential dynamics of histone post-translational modifications. The roles of histone modifying enzymes in this process, which are maternally provided, are only just starting to emerge. Here, we explore the function of the oocyte inherited pool of Lsd1/Kdm1a, which encodes a histone H3K4 and K9 demethylase, during early mouse development. Maternal deficiency of Lsd1/Kdm1a results in developmental arrest by the two-cell stage, associated with dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns depending on its demethylase activity. At the transcriptional level, two major changes occur. On one hand, switch from maternal-to-zygotic program fails to be induced. On the other hand, LINE-1 retrotransposons are not properly silenced, along with evidences for increased LINE-1 activity. We propose that Lsd1/Kdm1a is involved in the correct establishment of epigenetic information harboured by histones and is involved in the initiation of new pattern of genome expression driving early mouse development and preserving genome integrity Overall design: RNA-seq of invidual mouse two-cell stage embryos
Publication Title
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
How the parental genomes of the very specialized sperm and oocyte cells are remodelled upon fertilization to confer totipotency has remained a tantalizing open questions. Indeed, in the case of mammals, the parental genomes undergo dramatic reprogramming upon fertilization, including differential dynamics of histone post-translational modifications. The roles of histone modifying enzymes in this process, which are maternally provided, are only just starting to emerge. Here, we explore the function of the oocyte inherited pool of Lsd1/Kdm1a, which encodes a histone H3K4 and K9 demethylase, during early mouse development. Maternal deficiency of Lsd1/Kdm1a results in developmental arrest by the two-cell stage, associated with dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns depending on its demethylase activity. At the transcriptional level, two major changes occur. On one hand, switch from maternal-to-zygotic program fails to be induced. On the other hand, LINE-1 retrotransposons are not properly silenced, along with evidences for increased LINE-1 activity. We propose that Lsd1/Kdm1a is involved in the correct establishment of epigenetic information harboured by histones and is involved in the initiation of new pattern of genome expression driving early mouse development and preserving genome integrity Overall design: RNA-seq of invidual mouse oocytes
Publication Title
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Obesity is a major risk factor for metabolic disorders like insulin resistance and diabetes. We previously identified GPS2 as a clinical relavant repressor of metaflammation. No animal KO models were used to study its physiological function in vivo. The role of GPS2 in macrophage activation and inflammation is also largely unknown.
Publication Title
Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 9 Downloadable Samples
- NextSeq 500
Description
G1E cells infected with control (HMD empty vector), human GATA1, or human GATA1 mutant cDNA Overall design: 3 Biological replicates per condition for RNA-seq
Publication Title
Impaired human hematopoiesis due to a cryptic intronic <i>GATA1</i> splicing mutation.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FCGRIII) and chemokine receptors. Classical CD16- Mo express CCR2 and migrate in response to CCL2, while a minor CD16+ Mo subset expresses CX3CR1 and migrates into tissues expressing CX3CL1. CD16+ Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including HIV infection.
Publication Title
Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify molecules to serve as diagnostic markers for high-grade prostate cancer (PC) and targets for novel therapeutic drugs, we investigated the gene expression profiles of high-grade PCs using a cDNA microarray combined with laser microbeam microdissection.
Publication Title
The ubiquitin-like molecule interferon-stimulated gene 15 is overexpressed in human prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Classical CD16- versus intermediate/non-classical CD16+ monocytes differ in their homing potential and immunological functions; but whether they differentiate into dendritic cells (DC) with distinct contributions to immunity against bacterial/viral pathogens remains poorly investigated. Here, we employed a systems biology approach to identify differences between CD16+ and CD16- monocyte-derived DC (MDDC) with potential clinical relevance
Publication Title
CD16<sup>+</sup> monocytes give rise to CD103<sup>+</sup>RALDH2<sup>+</sup>TCF4<sup>+</sup> dendritic cells with unique transcriptional and immunological features.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The hallmark of IgA nephropathy (IgAN) is gross hematuria (GH) coinciding with or immediately following an upper respiratory or gastrointestinal tract infection and can represent the disease triggering event. Therefore, a whole genomic screening of IgAN patients during the GH was done to clarify the link between mucosal encountered antigens and the occurrence of glomerular hematuria. The modulated genes during GH show a clear involvement of the interferon signalling, antigen presenting pathway, and the immuno-proteasome. The gene characterizing cytotoxic effector lymphocytes (CX3CR1) implicated in vascular endothelial damage, was found up-regulated at both mRNA and protein level. In vitro antigenic stimulation of PBMCs on an independent set of IgAN patients and healthy blood donors (HBS) demonstrated that patients upregulate specifically CX3CR1 in an enhanced and dose dependant manner, while an expected down-regulation occurred in HBD. This enhanced activation occurred in both patients characterized by recurrent GH and by permanent microscopic hematuria (MH). We then analyzed glomerular fractalkine (FKN) expression, since this ligand is involved in the vascular gateway for CX3CR1+ cells towards the inflamed tissues. A significantly higher FKN expression on the capillary vessels and podocytes was found in recurrent GH patients compared to permanent MH, suggesting a predisposition for cytotoxic cell extravasation in recurrent GH patients.
Publication Title
Activated innate immunity and the involvement of CX3CR1-fractalkine in promoting hematuria in patients with IgA nephropathy.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples