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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 23, 2015 |
| Title |
Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 (ΔΨm). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-ΔΨm-sorted CD8+ T cells. Transfer of these low-ΔΨm T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-ΔΨm cells. Use of ΔΨm-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.
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| Overall design |
mRNA-Sequencing of gene expression profiles in mouse CD8 cells (TMRM high and TMRM low).
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| Contributor(s) |
Sukumar M, Liu J, Mehta GU, Patel SJ, Roychoudhuri R, Crompton JG, Klebanoff CA, JI Y, Li P, Yu Z, Whitehill GD, Clever D, Eil RL, Palmer D, Mitra S, Rao M, Keyvanfer K, Schrump D, Wang E, Marincola F, Gattinoni L, Leonard WJ, Muranski P, Finkel T, Restifo NP |
| Citation(s) |
26674251 |
| Submission date |
Oct 14, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Peng Li |
| E-mail(s) |
peng.li@nih.gov
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| Organization name |
NIH
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| Department |
NHLBI
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| Lab |
LMI
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| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA298695 |
| SRA |
SRP064796 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE74001_RAW.tar |
1.0 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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