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GSE136765
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
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.
Publication Title
The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing gene expression in ischemic, failing (F) to non-failing (NF) hearts. These results also were compared to the changes observed in a proteomic analysis of F and NF hearts.
Publication Title
Differential protein expression and basal lamina remodeling in human heart failure.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Cutaneous malignant melanoma is among the most deadly human cancers, broadly resistant to most clinical therapies. A majority of patients with BRAFV600E melanomas respond well to inhibitors such as vemurafenib, but all ultimately relapse. Moreover, there are no viable treatment options available for other non-BRAF melanoma subtypes in the clinic. A key to improving treatment options lies in a better understanding of mechanisms underlying melanoma progression, which are complex and heterogeneous. In this study we perform gene expression profilling of highly and poorly malignant melanocytic tumors from genetically engineered mouse models to discover important drivers of cancer progression.
Publication Title
Integrated Genomics Identifies miR-32/MCL-1 Pathway as a Critical Driver of Melanomagenesis: Implications for miR-Replacement and Combination Therapy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study, we demonstrate that hMSCs migrate toward human keratinocytes as well as toward conditioned medium from cultured human keratinocytes (KCM) indicating that the hMSCs can respond to signals from keratinocytes. Incubation of hMSCs with KCM induced dermal myofibroblast like differentiation characterized by expression of cytoskeletal markers vinculin and F-actin filaments with increased expression of alpha smooth muscle actin. We then examined the therapeutic efficacy of hMSCs in wound healing in two animal models representing normal and chronic wound healing. Accelerated wound healing, as determined by quantitative measurements of wound area, was observed when hMSCs and KCM exposed hMSCs (KCMSCs) were injected near the site of incisional/excisional wounds in nondiabetic athymic and NOD/SCID mice as compared with normal human fetal lung fibroblast WI38 cells or saline control induced wound healing.
Publication Title
Keratinocyte Induced Differentiation of Mesenchymal Stem Cells into Dermal Myofibroblasts: A Role in Effective Wound Healing.
Sample Metadata Fields
No sample metadata fields
View Samples- Oryza sativa
- 16 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Leaf samples were used. We exposed young seedlings to NaCl and drought.
Publication Title
Identification of cis-regulatory elements associated with salinity and drought stress tolerance in rice from co-expressed gene interaction networks.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Male Wistar rats weighing 90-120 g were acclimatized for one week and fed standard laboratory chow, at which time the animals were divided into two groups. Animals were then pair-fed for 8 weeks a regular laboratory chow and water ad libitum or Lieber-DeCarli diet (36% calories from ethanol). Control animals received the iso-caloric amount of dextrose to replace ethanol. After 8 weeks of differential feeding rats were euthanized, the pancreas immediately dissected and stored at -80?C until RNA isolation. RNA expression was analyzed using Affymetrix RAE230A gene chips
Publication Title
Long-term ethanol consumption alters pancreatic gene expression in rats: a possible connection to pancreatic injury.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Carcinoma associated fibroblasts (CAFs) have recently been implicated in important aspects of epithelial solid tumor biology such as neoplastic progression, tumor growth, angiogenesis, and metastasis. However, neither the source of CAFs nor the differences between CAFs and fibroblasts from non-neoplastic tissue have been well defined. In this study we demonstrate that human bone marrow-derived mesenchymal stem cells (hMSCs) exposed to tumor-conditioned medium (TCM) over a prolonged period of time assume a CAF-like myofibroblastic phenotype. More importantly, these cells exhibit functional properties of CAFs including sustained expression of stromal derived factor 1 (SDF-1) and the ability to promote tumor cell growth both in vitro and in an in vivo co-implantation model and expression of myofibroblast markers including -smooth muscle actin and fibroblast surface protein. hMSCs induced to differentiate to a myofibroblast-like phenotype using 5-azacytidine do not promote tumor cells growth as efficiently as hMSCs cultured in tumor-conditioned medium nor do they demonstrate increased SDF-1 expression. Furthermore, gene expression profiling revealed similarities between TCM exposed hMSCs and carcinoma associated fibroblasts. Taken together these data suggest that hMSCs are a source of carcinoma associated fibroblasts and can be used in the modeling of tumor-stroma interactions. To our knowledge this is the first report demonstrating that hMSCs become activated and resemble carcinoma associated myofibroblasts upon prolonged exposure to conditioned medium from MDAMB231 human breast cancer cells.
Publication Title
Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
Illumina HiSeq 2500
Description
The goals of this study are to compare NGS-derived whole transcriptome profiles (RNA-seq) of H5N1 infected A549 cells overexpressing either negative control mimic or miR-324-5p mimic Overall design: A549 cells were either mock transfected or transfected with either negative control or mir-324-5p mimic. After 12 hours cells were either mock infected (mock transfected cells) or infected with A/duck/India/02CA10/2011 - H5N1 virus (negative control and miR-324-5p overexpressing cells)
Publication Title
MicroRNA hsa-miR-324-5p Suppresses H5N1 Virus Replication by Targeting the Viral PB1 and Host CUEDC2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression profiling was carried out in six (wild type, ß2SP+/-, ß2SP-/-, SMAD3+/-, SMAD3-/- and ß2SP+/-/ SMAD3+/-) different mouse knockout embryonic fibroblast (MEF) cells. Beta-2-spectrin (ß2SP) is a dynamic intracellular non-pleckstrin homology (PH)-domain protein that belongs to a family of polypeptides that have been implicated in conferring cell polarity. Spectrins have been linked to multiple signaling pathways, including cell cycle regulation, DNA repair and TGFß signaling. In this study, we report a major role of the TGFß/Smad3 adaptor ß2-Spectrin in conserving genomic integrity from alcohol-induced DNA damage and describe a novel pathway that protects genomes from genotoxic stresses. To determine the mechanism for the oncogenic switch, and whether it is related to the role of ß2SP in TGF-ß signaling transduction or secondary to its cytoskeletal functions, we analyzed disruption of two elements of the TGF-ß pathway by generating double heterozygous Sptbn1+/-/Smad3+/- mice. Overall design: Whole-transcriptome RNA sequencing MEF cells of the following genotypes was carried out on an Illumina HiSeq 2000 sequencer: wildtype, heterozygous Beta-2-spectrin knockout (ß2SP+/-), homozygous Beta-2-spectrin knockout (ß2SP-/-), heterozygous SMAD3 (Mothers against decapentaplegic, Drosophila, Homolog of 3, SMAD3+/-), homozygous knockout SMAD3-/-, and double heterozygous mutation of Beta-2-spectrin and SMAD3 (ß2SP+/-/ SMAD3+/-).
Publication Title
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression profiling was carried out in two liver tumors and one normal liver isolated from ß2SP+/-; SMAD3+/- mice, and one normal liver isolated from wild type mouse. Whole-transcriptome sequencing of these 4 liver tissues. Overall design: Whole-transcriptome RNA sequencing of the 4 different samples
Publication Title
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples