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.
The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.
Sex, Specimen part
View SamplesThe Arabidopsis thaliana NAC domain transcription factor, VASCULAR-RELATED NAC-DOMAIN7 (VND7), acts as a key regulator of xylem vessel differentiation. In order to identify direct target genes of VND7, we performed global transcriptome analysis using Arabidopsis transgenic lines in which VND7 activity could be induced post-translationally. This analysis identified 63 putative direct target genes of VND7, which encode a broad range of proteins, such as transcription factors, IRREGULAR XYLEM proteins and proteolytic enzymes, known to be closely associated with xylem vessel formation. Recombinant VND7 protein binds to several promoter sequences present in candidate direct target genes: specifically, in the promoter of XYLEM CYSTEINE PEPTIDASE1, two distinct regions were demonstrated to be responsible for VND7 binding. We also found that expression of VND7 restores secondary cell wall formation in the fiber cells of inflorescence stems of nst1nst3 double mutants, as well as expression of NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3, however, the vessel-type secondary wall deposition was observed only as a result of VND7 expression. These findings indicated that VND7 upregulates, directly and/or indirectly, many genes involved in a wide range of processes in xylem vessel differentiation, and that its target genes are partially different from those of NSTs.
VASCULAR-RELATED NAC-DOMAIN7 directly regulates the expression of a broad range of genes for xylem vessel formation.
Age, Specimen part, Treatment
View SamplesMultidrug resistance (MDR) frequently develops in cancer patients exposed to chemotherapeutic agents and is usually brought about by over-expression of P-glycoprotein (P-gp) which acts as a drug efflux pump. MiRNAome profiling using next-generation sequencing identified differentially expressed microRNAs (miRs) between parental K562 cells and MDR K562 cells (K562/ADM) induced by chronic adriamycin treatment. Overall design: MiRNAome profiling in untreated K562 cells and K562 cells exposed to long-term adriamycin treatment
Changes in the expression of miR-381 and miR-495 are inversely associated with the expression of the MDR1 gene and development of multi-drug resistance.
No sample metadata fields
View SamplesWe investigated morphometric structure and gene expression by microarray analysis in a small diameter artery, branch of the saphenous artery (a resistance artery), in representative models of renin-angiotensin system (RAS)-dependent and glucocorticoid hypertension, using the spontaneously hypertensive rat (SHR) and adrenocorticotropic hormone (ACTH)-induced hypertensive rat, respectively.
Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets.
No sample metadata fields
View SamplesWe established a novel in vitro tissue culture system (named VISUAL), in which xylem and phloem differentiation can be induced with Arabidopsis thaliana cotyledons
Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.
Age, Specimen part, Time
View SamplesWe established a novel in vitro tissue culture system (named VISUAL), in which xylem and phloem differentiation can be induced with Arabidopsis thaliana cotyledons
Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.
Specimen part, Time
View SamplesThe transcript levels of 560 genes were decreased (less than two-fold), while those of 312 genes were increased (more than two-fold) in the KO-HsfA1d/A1e plants compared with the wild-type plants. The transcript levels of HsfA2, HsfA7a, HsfA7b, HsfB1, and HsfB2a were down-regulated in the KO-HsfA1d/A1e
HsfA1d and HsfA1e involved in the transcriptional regulation of HsfA2 function as key regulators for the Hsf signaling network in response to environmental stress.
Specimen part
View SamplesTo explore how PKC regulates tumorigenesis, we performed mRNA expression analysis of four KRAS mutant NSCLC cell lines that stably express scrambled shRNA or PKC targeted shRNA
PKCδ regulates integrin αVβ3 expression and transformed growth of K-ras dependent lung cancer cells.
Disease, Cell line, Treatment
View SamplesWe evaluated the effect of NORAD (also known as LINC00657 or LOC647979) shRNA on TGF-beta induced changes in the gene expression in A549 cells by RNA-seq. Overall design: mRNA expression was determined in a lung adenocarcinoma cancer cell line A549 infected with NORAD shRNA-expressing lentiviral vector and treated with TGF-beta.
Long noncoding RNA NORAD regulates transforming growth factor-β signaling and epithelial-to-mesenchymal transition-like phenotype.
Cell line, Subject
View SamplesInduced pluripotent stem cell (iPSC) technology allows for the generation of patient-specific pluripotent stem cells, from somatic cell sources, thereby providing a novel cell therapy platform for severe degenerative diseases. One of the key issues for clinical-grade iPSC derivation is the accessibility of donor cells used for reprogramming and subsequent feasiblity of reprogramming into a pluripotent state.
Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells.
Specimen part
View Samples