Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Single cell RNA-seq of individual cells from dorsal skin of a F1 mouse cross-breed (C57BL/6JxCAST/EiJ)

ABSTRACT: Sequencing of diverse cell types present in the dorsal skin of a F1 mouse cross-breed in order to study the regulation of transcription on an allele-resolved level.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Rickard Sandberg

PROVIDER: E-MTAB-12181 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptional bursts explain autosomal random monoallelic expression and affect allelic imbalance.

Larsson Anton J M AJM Ziegenhain Christoph C Hagemann-Jensen Michael M Reinius Björn B Jacob Tina T Dalessandri Tim T Hendriks Gert-Jan GJ Kasper Maria M Sandberg Rickard R

PLoS computational biology 20210309 3

Transcriptional bursts render substantial biological noise in cellular transcriptomes. Here, we investigated the theoretical extent of allelic expression resulting from transcriptional bursting and how it compared to the amount biallelic, monoallelic and allele-biased expression observed in single-cell RNA-sequencing (scRNA-seq) data. We found that transcriptional bursting can explain the allelic expression patterns observed in single cells, including the frequent observations of autosomal monoa ...[more]

PMID: 33690599

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Project description:Background Clinical success of T cell receptor (TCR) gene therapy has previously been demonstrated for NY-ESO-1 TCR gene therapy. To increase numbers of cancer patients that can be treated with TCR gene therapy we aimed to identify a novel set of high-affinity cancer specific TCRs targeting different cancer testis (CT) antigens in prevalent HLA class I alleles. Methods In this study, we selected based on publicly available gene expression databases the most promising CT genes to target. From these selected genes we identified by HLA peptidomics the naturally processed and presented HLA class I peptides. With these peptide-HLA tetramers were generated, and by single cell sorting CT specific CD8+ T cells were selected, and expanded from the allo-HLA repertoire of healthy donors. By several functional assays high avidity CT-specific T cell clones with safe recognition pattern were selected. To evaluate the potential for clinical application in TCR gene therapy, TCRs were sequenced and transferred into peripheral blood derived CD8+ T cells. Results In total we identified, 7 novel CT-specific TCRs that effectively target MAGE-A1, MAGE-A3, MAGE-A6 and MAGE-A9 in the context of human leukocyte antigen(HLA) -A1, -A2, -A3, -B7, -B35 and -C7. TCR gene transfer into CD8⁺ T cells resulted in efficient cytokine production and cytotoxicity of variety of different tumor types without detectable cross-reactivity. In addition, major in vivo antitumor effects of MAGE-A1 specific TCR engineered CD8⁺ T cells was observed in an orthotopic xenograft model for established multiple myeloma, in which bone marrow located tumor cells were completely eradicated after T cell injection. Conclusion The identification of 7 novel CT-specific TCRs, reactive against CT antigens presented in a variety of different HLA class I alleles, allows selection of therapeutic TCRs for an increased number of cancer patients, and will improve development of personalized TCR gene therapy.

Dataset Information

Single cell RNA-seq of individual cells from dorsal skin of a F1 mouse cross-breed (C57BL/6JxCAST/EiJ)

Publications

Transcriptional bursts explain autosomal random monoallelic expression and affect allelic imbalance.

Similar Datasets

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