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

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

PROVIDER: PRJNA497195 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12244200_1.fastq.gz	Fastqsanger.gz
	SRR12244200_2.fastq.gz	Fastqsanger.gz
	SRR12244201_1.fastq.gz	Fastqsanger.gz
	SRR12244201_2.fastq.gz	Fastqsanger.gz
	SRR12244202_1.fastq.gz	Fastqsanger.gz

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

Project description:Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors [iR_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 [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.

2020-07-31 | GSE121371 | GEO

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

Project description:We identified that the coordinated expression of exogenous transcription factors(Lhx2, Hoxa9, and Runx1), efficiently guides PSC-derived hematopoietic progenitors (iHPC) preferentially towards B cell lineage commitment, which successfully regenerate B lymphopoiesis in B-cell deficient animals. Of note, the abundancy of in vivo lymphopoiesis includes pro/pre-B progenitors, immature B cells, and all subsets of mature B1a, B1b, FO B and MZ B reconstitution in vivo. We performed single-cell RNA-Seq using the sorted GFP+CD45+ Lin- cells from the bone marrow of recipients at day 7.5 after iHPC transplantation.

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Project description:Arterial endothelial cells (AECs) are the founder cell for intraembryonic haematopoiesis. Here, we report a method for the efficient generation of human haemogenic DLL4+ AECs from pluripotent stem cells (PSC). Time-series single cell RNA-sequencing revealed the dynamic evolution of haematopoiesis and lymphopoiesis from endothelial stage, generating cell types with counterparts present in early human embryos. Our study describes an efficient method for producing lymphoid cells and provides insights into their endothelial and haematopoietic ontogeny, paving a new path to investigations of the human blood system.

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Human arterial endothelial cells from pluripotent stem cells for in vitro hematopoiesis and lymphopoiesis

Project description:Human arterial endothelial cells from pluripotent stem cells for in vitro hematopoiesis and lymphopoiesis

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

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