Haematopoietic stem and progenitor cells from human pluripotent stem cells

Ryohichi Sugimura, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz da Rocha, Yi-Fen Lu, Jeremy A. Goettel, Erik Serrao, R. Grant Rowe, Mohan Malleshaiah, Irene Wong, Patricia Sousa, Ted N. Zhu, Andrea Ditadi, Gordon Keller, Alan N. Engelman, Scott B. Snapper, Sergei Doulatov and George Q. Daley ()
Additional contact information
Ryohichi Sugimura: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
Deepak Kumar Jha: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
Areum Han: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
Clara Soria-Valles: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
Edroaldo Lummertz da Rocha: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
Yi-Fen Lu: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
Jeremy A. Goettel: Hepatology and Nutrition, Boston Children’s Hospital
Erik Serrao: Harvard Medical School
R. Grant Rowe: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
Mohan Malleshaiah: Harvard Medical School
Irene Wong: Brandeis University
Patricia Sousa: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
Ted N. Zhu: Program in Computer Science, Harvard University
Andrea Ditadi: McEwen Centre for Regenerative Medicine, University Health Network
Gordon Keller: McEwen Centre for Regenerative Medicine, University Health Network
Alan N. Engelman: Harvard Medical School
Scott B. Snapper: Hepatology and Nutrition, Boston Children’s Hospital
Sergei Doulatov: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
George Q. Daley: Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute

Nature, 2017, vol. 545, issue 7655, 432-438

Abstract: Abstract A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders.

Date: 2017
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DOI: 10.1038/nature22370

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