Long-term survival and antitumor immunity of adoptively transferred CD8+ T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established. Here we utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (??m). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-??m-sorted CD8+ T cells. Transfer of these low-??m T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-??m cells. Use of ??m-based sorting to enrich for cells with superior metabolic features was observed in CD8+, CD4+ T cell subsets, and long-term hematopoietic stem cells. This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viral-associated illnesses and cancer. Overall design: mRNA-Sequencing of gene expression profiles in mouse CD8 cells (TMRM high and TMRM low).
Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy.
Specimen part, Cell line, Subject
View SamplesSV40 transforms cells through the action of two oncoproteins, large T antigen and small t antigen. Small t antigen targets phosphatase PP2A, while large T antigen stimulates cell proliferation and survival by action on multiple proteins, including the tumor suppressors Rb and p53. Large T antigen also binds components of the transcription initiation complex and several transcription factors. We examined global gene expression in SV40-transformed mouse embryo fibroblasts, and in enterocytes obtained from transgenic mice. SV40 transformation alters the expression of approximately 800 cellular genes in both systems. Much of this regulation is observed in both MEFs and enterocytes and is consistent with T antigen action on the Rb-E2F pathway. However, the regulation of many genes is cell-type specific, suggesting that unique signaling pathways are activated in different cell types upon transformation, and that the consequences of SV40 transformation depends on the type of cell targeted.
Cell-type specific regulation of gene expression by simian virus 40 T antigens.
No sample metadata fields
View SamplesHSC (Sca+ SP) were isolated from 8-12 week C57B6 mice at various time points after treatment with 5-Fluorouracil. RNA was isolated from 50,000-100,000 FACS sorted cells and subjected to two rounds of T7 based linear amplification using Ambion's Message Amp kit. Two replicates from each time point were analyzed.
Molecular signatures of proliferation and quiescence in hematopoietic stem cells.
No sample metadata fields
View SamplesPemetrexed is an antifolate drug used in the treatment of lung cancer. EA.hy 926 cells grown under low (Lo) and normal (Hi) folate conditions were treated with PMX. Microarray analysis was used to examine changes in gene expression due to PMX treatment.
Pemetrexed alters folate phenotype and inflammatory profile in EA.hy 926 cells grown under low-folate conditions.
Cell line
View SamplesT lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8a+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology. Overall design: GFP- CD3e+ CD8a+ CD4-, GFP- CD3e+ CD8a- CD4+ CD25- and GFP- CD3e+ CD8a- CD4+ CD25+ T cells were isolated from spleens of UBC-GFP mice transplanted with WT or cDKO lineage-depleted donor bone marrow following lethal irradiation of recipient mice. RNA-seq was performed on 3-4 biological replicates from each genotype for all T cell populations analyzed.
Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs.
Specimen part, Cell line, Subject
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View SamplesAtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Specimen part
View Samples