論文 - 詳細
| RRC ID | 78712 |
|---|---|
| 著者 | Lu X, Lofgren SM, Zhao Y, Mazur PK. |
| タイトル | Multiplexed transcriptomic profiling of the fate of human CAR T cells in vivo via genetic barcoding with shielded small nucleotides. |
| ジャーナル | 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. |
| 巻・号 | 7(9) |
| ページ | 1170-1187 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 22 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | K562(RCB0027) NALM-6(RCB1933) |