Generation of transgene-free hematopoietic stem cells from human induced pluripotent stem cells - Evolution Paris Seine
Journal Articles Cell Stem Cell Year : 2023

Generation of transgene-free hematopoietic stem cells from human induced pluripotent stem cells

Mathias Brunet-Manquat
  • Function : relator_co_first_author

Abstract

Hematopoietic stem cells (HSCs) are the rare cells responsible for the lifelong curative effects of hematopoietic cell (HC) transplantation. The demand for clinical-grade HSCs has increased significantly in recent decades, leading to major difficulties in treating patients. A promising but not yet achieved goal is the generation of HSCs from pluripotent stem cells. Here, we have obtained vector- and stroma-free transplantable HSCs by differentiating human induced pluripotent stem cells (hiPSCs) using an original one-step culture system. After injection into immunocompromised mice, cells derived from hiPSCs settle in the bone marrow and form a robust multilineage, hematopoietic population that can be serially transplanted. Single cell RNA sequencing shows that this repopulating activity is due to a hematopoietic population that is transcriptionally similar to human embryonic aorta-derived HSCs. Overall, our results demonstrate the generation of HSCs from hiPSC and will help identify key regulators of HSC production during human ontogeny.
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hal-04355216 , version 1 (09-01-2024)

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Olivier Piau, Mathias Brunet-Manquat, Laurence Petit, Bruno L'Homme, Brigitte Birebent, et al.. Generation of transgene-free hematopoietic stem cells from human induced pluripotent stem cells. Cell Stem Cell, 2023, 30 (12), pp.1610-1623.e7. ⟨10.1016/j.stem.2023.11.002⟩. ⟨hal-04355216⟩
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