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Status |
Public on Aug 20, 2019 |
Title |
Organoid-induced differentiation of conventional T cells from human pluripotent stem cells |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Generation of T cells from pluripotent stem cells (PSC) has the potential to transform adoptive immunotherapy for cancer into universal donor, off-the-shelf cellular therapies. However, differentiation of human PSCs into fully mature T cells has been challenging with existing methods. We report that a 3D organoid method permitted efficient differentiation of human embryonic stem cell and induced pluripotent stem cell-derived mesoderm progenitors to mature, functional conventional T cells with a diverse T cell receptor (TCR) repertoire. This continuous culture system supported both hematopoietic induction and terminal differentiation to naïve, conventional CD3+CD8αβ+ and CD3+CD4+ T cells. Introduction of a Class I-restricted TCR in PSCs produced antigen-specific CD8αβ+ T cells lacking endogenous TCR expression. Functional assays and RNA sequencing aligned PSC-derived T cells with primary naïve conventional CD8+ T cells. The organoid system presented here provides an effective and scalable platform to generate functional mature T cells from human PSCs.
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Overall design |
Our goal was to analyze and compare transcriptome of human naïve T cells generated in Artificial Thymic Organoids (ATOs) from PSC with human naïve T cells from thymus and Cord blood ATOs.
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Contributor(s) |
Montel-Hagen A, Seet CS, Li S, Chick B, Zhu Y, Chang P, Lopez S, Tsai S, He CB, Chin CJ, Casero D, Crooks GM |
Citation(s) |
30661959 |
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Submission date |
Jun 19, 2018 |
Last update date |
Aug 20, 2019 |
Contact name |
Gay Miriam Crooks |
E-mail(s) |
gcrooks@mednet.ucla.edu
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Phone |
3102060205
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Organization name |
University of California Los Angeles
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Department |
Pathology & Laboratory Med
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Street address |
610 Charles E. Young Drive, East
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City |
Los Angeles |
State/province |
California |
ZIP/Postal code |
90095 |
Country |
USA |
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Platforms (1) |
GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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Samples (32)
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Relations |
BioProject |
PRJNA476793 |
SRA |
SRP150879 |