Role of Notch signaling on hematopoietic stem cell differentiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11723 | GEO | 2009/06/02
SECONDARY ACCESSION(S): PRJNA106021
REPOSITORIES: GEO
Similar Datasets
Project description:To assess the effect of over-expression of Delta-like 1 on OP9 cells on gene expression in terms of Notch signaling and adhesion molecules, gene expressions of OP9, OP9-GFP (carrying GFP gene) and OP9-DL1 (carrying GFP and DL1 gene) cells (Immunity 2002;17:749-756) were analyzed.
2010-10-01 | GSE22659 | GEO
Project description:To assess the effect of over-expression of Delta-like 1 on OP9 cells on gene expression in terms of Notch signaling and adhesion molecules, gene expressions of OP9, OP9-GFP (carrying GFP gene) and OP9-DL1 (carrying GFP and DL1 gene) cells (Immunity 2002;17:749-756) were analyzed. Gene expression of OP9, OP9-GFP and OP9-DL1 were compared.
2010-10-01 | E-GEOD-22659 | biostudies-arrayexpress
Project description:ODE model describing how slight variations in Notch and Delta cellular concentrations, through lateral inhibition, lead to cells with different states of differentiation. Lateral inhibition is a process whereby a given cell adopting a given fate prevents its immediate neighbouring cells from doing likewise. Notch and Delta are interacting transmembrane proteins and according to this model, lateral inhibition is due to a process where the inhibited cells (where notch has been activated by Delta) loose their ability to inhibit other cells (by synthesizing Delta). This process creates a feedback loop where cells with more delta proteins on their surface inhibit their immediate neighbours and adopt a different cell fate than those neighbours.
2022-04-05 | BIOMD0000001047 | BioModels
Project description:The IRF8-dependent subset of classical dendritic cells (cDC), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor Flt3 ligand (Flt3L) yields very few cDC1 (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing Notch ligand Delta-like 1 (OP9-DL1) optimize Flt3L-driven development of cDC1 from murine immortalized progenitors and primary bone marrow cells. Co-culture with OP9-DL1 induced IRF8-dependent cDC1 with the phenotype (CD103+ Dec205+ CD8α+) and expression profile resembling ex vivo cDC1. OP9-DL1-induced cDC1 showed preferential migration towards Ccr7 ligands in vitro and superior T cell cross-priming and antitumor vaccination in vivo. Co-culture with OP9-DL1 also greatly increased the yield of IRF8-dependent CD141+ cDC1 from human bone marrow progenitors cultured with Flt3L. Thus, Notch signaling optimizes cDC generation in vitro and yields authentic cDC1 for functional studies and therapeutic applications.
2018-06-05 | GSE110577 | GEO
Project description:We used microarrays to perform a global gene expression analysis in Tcf1-expressing Thy1+CD25+ T lineage cells that develop on OP9 stroma in the absence of Notch1 signals. We compare this to the starting population, LMPP progenitors, and to control expressing T lineage cells that developed on OP9 stroma expressing Notch ligand DL4. The overall goal of this study was to determine if Tcf1 initiates T lineage specification in lymphoid progenitors. We found that Tcf1 was sufficient to upregulate many T lineage genes as compared to control expressing progenitors on OP9-DL4. Abstract of manuscript: The thymus imposes the T cell fate on incoming multipotent progenitors, but the molecular mechanisms are poorly understood. We show that transcription factor Tcf1 initiates T-lineage-specific gene expression. Tcf1 is downstream of Notch1 signaling and expressed in early T-cell progenitors. Progenitors deficient for Tcf1 are unable to initiate normal T-lineage specification. Conversely, ectopic expression of Tcf1 in hematopoietic progenitors is sufficient to induce expression of T-lineage specific genes in vitro. Thus, our study identifies Tcf1 as critically involved in the establishment T cell identity. Wiltype LMPPs were isolated by a FACSAria cell sorter and retrovirally transduced with a Tcf1-containing (Tcf1-VEX) or control vector (VEX) retrovirus. Tcf1-expressing cells and control-vector expressing cells were then seeded on OP9 stroma or OP9 stroma expressing Notch ligand DL4, respectively. On day 10, Thy1+CD25+ T lineage cells were sorted from Tcf1-expressing cells on OP9 stroma and compared to sorted LMPPs and Thy1+CD25+ T lineage cells that developed from control-vector expressing cells on OP9-DL4.
2011-08-03 | E-GEOD-26560 | biostudies-arrayexpress
Project description:Recent studies have shown that stem cell memory T (TSCM) cell-like properties are important for the successful adoptive immune therapy by the chimeric antigen receptor-engineered-T (CAR-T) cells. We previously reported that both human and murine activated T cells are converted into stem cell memory-like T (iTSCM) cells by co-culture with stromal OP9 cells expressing the NOTCH-ligand. However, the mechanism of NOTCH-mediated iTSCM reprogramming remains to be elucidated. Here, we report that the NOTCH/OP9 system efficiently converts conventional human CAR-T cells into TSCM-like CAR-T, “CAR-iTSCM” cells, and that the mitochondrial metabolic reprogramming plays a key role in this conversion. The NOTCH signals promote mitochondrial biogenesis and fatty acid synthesis during iTSCM formation, which are essential for the properties of iTSCM cells. We identified fork head box M1 (FOXM1) as a downstream target of NOTCH, which is responsible for these metabolic changes and the subsequent iTSCM differentiation. Like NOTCH-induced CAR-iTSCM cells, FOXM1-induced CAR-iTSCM cells possess superior antitumor potential compared to conventional CAR-T cells. We propose that the NOTCH- or FOXM1-driven CAR-iTSCM formation is an effective strategy for improving cancer immunotherapy.
2019-09-04 | GSE136765 | GEO
Project description:Hypoxia (low oxygen) and Notch signaling are two important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increases Notch signaling, in a process requiring the vasoactive hormone adrenomedullin but not endogenous VEGF. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, functional Notch signaling was required for hypoxia to upregulate the arterial marker genes Depp, connexin40 (Gja5), Cxcr4 and Hey1. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxiamediated induction of the arterial differentiation program. 12 microarray samples consisting of >50,000 FACS sorted CD31+ cells purified from wild type mouse CCE ES cells that were differentiated into the endothelial lineages in 3 biological replicates. The ES cells were subjected to embryoid body formation over 4 days in hanging drop cultures, FACS sorted for Flk1 positive vascular progenitors cells and plated for a further 4 days in normoxia (21% oxygen) or hypoxia (1.5-2% oxygen) with or without 4 umol/l gamma-secretase inhibitor L-685.458.
2013-02-08 | E-GEOD-35894 | biostudies-arrayexpress
Project description:The stepwise conversion of multipotent precursors into committed T-cell progenitors depends on several transcriptional regulators, but the interplay between these factors is still obscure. This is particularly true in human since the core early Notch signalling pathway also supports NK cell development and requires tight regulation for efficient T-lineage commitment and differentiation. Here, we show that GATA3, in contrast to TCF1, induces T-lineage commitment following NOTCH1-induced T-lineage specification through direct regulation of at least 3 distinct processes: repression of NK-cell fate, activation of T-lineage genes to promote further differentiation, and downmodulation of Notch signalling activity. GATA3-mediated repression of the NOTCH1 target gene DTX1 hereby is essential to induce T-lineage commitment at the expense of NK cell differentiation. Thus, human T-lineage commitment is dependent on the precise collaboration of several transcriptional regulators that integrate through both positive and negative regulatory loops. Gene expression was profiled in CT CD34+ cells after transduction with control or GATA3 and coculture on OP9-DL1 for 48h. Cells were collected 48h after coculture and sorted for CD45+EGFP+. 3 independent experiments were performed on 3 different thymus donors.
2016-04-06 | E-GEOD-71752 | biostudies-arrayexpress
Project description:Summary Purpose: By means of high-throughput data analysis (high-throughput sequencing or next-generation sequencing -NGS-), we addressed the effect of the absence of Ikaros and the Notch pathway activation in mouse fetal liver erythroid cells. Specifically, the goals of this study are (i) to characterize the transcriptome of erythroid cells in the absence of Ikaros, when the Notch pathway is activated or not (by RNA-seq); (ii) to identify patterns in the modification of gene regulation according to the variable conditions; and (iii) to obtain information on mechanisms involved in the variation of gene regulation. Methods: Erythroid cells obtained from Ikaros wild type (WT) or Ikaros knockout (Null) mouse fetal livers at the embryonic stage e14.5. These cells were co-cultured for 48 h on OP9 or OP9-DL1 cells. mRNA profiles were generated by NGS, in biological triplicate, using Illumina cBot 2 System. The quality of the raw reads was assessed with FASTQC. Report show no pool imbalance. After examining the quality of the raw reads, no trimming was deemed necessary. The reads were aligned to the GRCm38/mm10 genome with TopHat. The raw alignment counts were calculated with htseq-count. DESeq2 calculates the differential expression of genes directly from the raw alignment counts calculated with htseq-count. The output from DESeq2 includes the raw counts normalized relative to the total number of reads. The log2 fold change is an estimate of the fold change between the conditions, based on the distribution of the reads. qRT-PCR validation was performed using specific primer sets in real-time PCR with SYBR Green. Results. Based on expression profiles, all samples clustered correctly. The differential expression analysis was perform with all samples. For subsequent analysis, 2452 differentially expressed genes were identified in Ikaros WT vs Ikaros null cells cultured on OP9 cells, using a log2 ≥ 1 and a p value <0.005. Additionally, 2847 differentially expressed genes were identified in Ikaros WT vs Ikaros Null cells cultured on OP9-DL1 cells, using a log2 ≥ 1 and a p value <0.005. Among genes activated by Notch (cells cultured on OP9-DL1), 616 genes were repressed in the absence of Ikaros (Ikaros Null vs WT cells; log2≥ -0.8 and a p value <0.005) and 1558 genes were overexpressed in in the absence of Ikaros (Ikaros Null vs WT cells: log2≥ 0.8 and a p value <0.005), using adjusted p value <0.005. Modified expression or immunoprecipitation of several gene transcripts was confirmed with qRT-PCR. Conclusions (Summary): The results obtained demonstrate that Ikaros can favour repression of Notch target genes but can also be required for proper activation on Notch targets upon Notch pathway activation.
2020-12-18 | GSE122951 | GEO
Project description:We have manipulated the NOTCH signaling pathway in mouse embryonic endocardial cells by the co-culture with OP9 stromal cells expressing Jag1 and Dll4, the culture over recombinant JAG1 and DLL4, and the use of the γ-secretase inhibitor RO4929097. We have performed RNA-seq and ATAC-seq to define the transcriptional profile and the chromatin accessibility landscape specific for each condition.
2023-12-08 | GSE223735 | GEO