Reference - Detail
| RRC ID | 78712 |
|---|---|
| Author | Lu X, Lofgren SM, Zhao Y, Mazur PK. |
| Title | Multiplexed transcriptomic profiling of the fate of human CAR T cells in vivo via genetic barcoding with shielded small nucleotides. |
| Journal | Nat Biomed Eng |
| Abstract |
The design of chimeric antigen receptor (CAR) T cells would benefit from knowledge of the fate of the cells in vivo. This requires the permanent labelling of CAR T cell products and their pooling in the same microenvironment. Here, we report a cell-barcoding method for the multiplexed longitudinal profiling of cells in vivo using single-cell RNA sequencing (scRNA-seq). The method, which we named shielded-small-nucleotide-based scRNA-seq (SSN-seq), is compatible with both 3' and 5' single-cell profiling, and enables the recording of cell identity, from cell infusion to isolation, by leveraging the ubiquitous Pol III U6 promoters to robustly express small-RNA barcodes modified with direct-capture sequences. By using SSN-seq to track the dynamics of the states of CAR T cells in a tumour-rechallenge mouse model of leukaemia, we found that a combination of cytokines and small-molecule inhibitors that are used in the ex vivo manufacturing of CAR T cells promotes the in vivo expansion of persistent populations of CD4+ memory T cells. By facilitating the probing of cell-state dynamics in vivo, SSN-seq may aid the development of adoptive cell therapies. |
| Volume | 7(9) |
| Pages | 1170-1187 |
| Published | 2023-9-1 |
| DOI | 10.1038/s41551-023-01085-3 |
| PII | 10.1038/s41551-023-01085-3 |
| PMID | 37652986 |
| MeSH | Animals CD4-Positive T-Lymphocytes* Cell- and Tissue-Based Therapy Cytokines Humans Mice Nucleotides Transcriptome* |
| IF | 18.952 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 22 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | K562(RCB0027) NALM-6(RCB1933) |