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Organoid-induced differentiation of conventional T cells from human pluripotent stem cells

ABSTRACT: Organoid-induced differentiation of conventional T cells from human pluripotent stem cells

PROVIDER: PRJNA476793 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7369120_1.fastq.gz	Fastqsanger.gz
	SRR7369120_2.fastq.gz	Fastqsanger.gz
	SRR7369130_1.fastq.gz	Fastqsanger.gz
	SRR7369130_2.fastq.gz	Fastqsanger.gz
	SRR7369140_1.fastq.gz	Fastqsanger.gz

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Organoid-induced differentiation of conventional T cells from human pluripotent stem cells

Project description: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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Organoid-Induced Differentiation of Conventional T Cells from Human Pluripotent Stem Cells.

Project description:The ability to generate T cells from pluripotent stem cells (PSCs) has the potential to transform autologous T cell immunotherapy by facilitating universal, off-the-shelf cell products. However, differentiation of human PSCs into mature, conventional T cells has been challenging with existing methods. We report that a continuous 3D organoid system induced an orderly sequence of commitment and differentiation from PSC-derived embryonic mesoderm through hematopoietic specification and efficient terminal differentiation to naive CD3+CD8αβ+ and CD3+CD4+ conventional T cells with a diverse T cell receptor (TCR) repertoire. Introduction of an MHC class I-restricted TCR in PSCs produced naive, antigen-specific CD8αβ+ T cells that lacked endogenous TCR expression and showed anti-tumor efficacy in vitro and in vivo. Functional assays and RNA sequencing aligned PSC-derived T cells with primary naive CD8+ T cells. The PSC-artificial thymic organoid (ATO) system presented here is an efficient platform for generating functional, mature T cells from human PSCs.

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