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Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors [iR_iHEC]

ABSTRACT: Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors [iR_iHEC]

PROVIDER: PRJNA531384 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12244100_1.fastq.gz	Fastqsanger.gz
	SRR12244100_2.fastq.gz	Fastqsanger.gz
	SRR12244101_1.fastq.gz	Fastqsanger.gz
	SRR12244101_2.fastq.gz	Fastqsanger.gz
	SRR12244102_1.fastq.gz	Fastqsanger.gz

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Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors [single hematopoietic cells (iHEC)]

Project description:Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors [single hematopoietic cells (iHEC)]

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Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors.

Project description:Achievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells (PSCs) is a central aim in T cell regenerative medicine. To date, preferentially reconstituting T lymphopoiesis in vivo from PSCs remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial-to-hematopoietic transition and hematopoietic maturation stages in a PSC differentiation scheme (iR9-PSC) in vitro induced preferential generation of engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSCs, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The induced T cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis restored immune surveillance in immunodeficient mice. Furthermore, gene-edited iR9-PSCs produced tumor-specific T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T cells from the unlimited and editable PSC source.

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Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors [iR_iHEC]

Project description:We inserted the inducible expression cassette of Runx1 into the Rosa26 locus of embryonic stem cells. Based on a modified protocol for HEC induction from PSC, we successfully generated iHEC Under the haematopoietic induction process (iR-HEC).

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Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors

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T cell regeneration from pluripotent stem cells by defined transcription factors

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Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors [single hematopoietic cells (iHEC)]

Project description:We identified that the coordinated expression of exogenous Runx1 and Hoxa9 during the haematopoietic induction process from mouse PSC resulted in a type of induced hemogenic endothelial cells (iHEC). The single iHEC can be robustly educated into induced haematopoietic progenitor cells (iHPC), which gave rise to induced T cells (iT cells) with abundant TCRαβ repertoire in vivo. We sorted the single iHEC and iHPC from day-14, day-17, day-21 cell products derived from 241 iR9-ES and performed single-cell RNA-Seq.

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Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors

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2021-12-16 | GSE180319 | GEO

Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors

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