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Haematopoietic stem and progenitor cells from human pluripotent stem cells

Author

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  • Ryohichi Sugimura

    (Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Stem Cell Institute
    Manton Center for Orphan Disease Research)

  • Deepak Kumar Jha

    (Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Stem Cell Institute
    Manton Center for Orphan Disease Research)

  • Areum Han

    (Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
    Harvard Medical School)

  • Clara Soria-Valles

    (Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Stem Cell Institute
    Manton Center for Orphan Disease Research)

  • Edroaldo Lummertz da Rocha

    (Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Stem Cell Institute
    Manton Center for Orphan Disease Research)

  • Yi-Fen Lu

    (Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Stem Cell Institute
    Manton Center for Orphan Disease Research)

  • Jeremy A. Goettel

    (Hepatology and Nutrition, Boston Children’s Hospital
    Harvard Medical School)

  • 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
    Harvard Medical School
    Harvard Stem Cell Institute
    Manton Center for Orphan Disease Research)

  • 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
    Harvard Medical School
    Brigham and Women’s Hospital)

  • Sergei Doulatov

    (Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Stem Cell Institute
    Manton Center for Orphan Disease Research)

  • George Q. Daley

    (Stem Cell Transplantation Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Stem Cell Institute
    Manton Center for Orphan Disease Research)

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.

Suggested Citation

  • 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 & Patr, 2017. "Haematopoietic stem and progenitor cells from human pluripotent stem cells," Nature, Nature, vol. 545(7655), pages 432-438, May.
    • Handle: RePEc:nat:nature:v:545:y:2017:i:7655:d:10.1038_nature22370
    DOI: 10.1038/nature22370
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    Citations

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    Cited by:

    1. Yinghui Li & Mei He & Wenshan Zhang & Wei Liu & Hui Xu & Ming Yang & Hexiao Zhang & Haiwei Liang & Wenjing Li & Zhaozhao Wu & Weichao Fu & Shiqi Xu & Xiaolei Liu & Sibin Fan & Liwei Zhou & Chaoqun Wan, 2023. "Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Pierre Sabatier & Christian M. Beusch & Amir A. Saei & Mike Aoun & Noah Moruzzi & Ana Coelho & Niels Leijten & Magnus Nordenskjöld & Patrick Micke & Diana Maltseva & Alexander G. Tonevitsky & Vincent , 2021. "An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Patrick Coulombe & Grace Cole & Amanda Fentiman & Jeremy D. K. Parker & Eric Yung & Misha Bilenky & Lemlem Degefie & Patrick Lac & Maggie Y. M. Ling & Derek Tam & R. Keith Humphries & Aly Karsan, 2023. "Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Pragya Gupta & Sangam Giri Goswami & Geeta Kumari & Vinodh Saravanakumar & Nupur Bhargava & Akhila Balakrishna Rai & Praveen Singh & Rahul C. Bhoyar & V. R. Arvinden & Padma Gunda & Suman Jain & Vanya, 2024. "Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Shuyang Cai & Honghu Li & Ruxiu Tie & Wei Shan & Qian Luo & Shufen Wang & Cong Feng & Huiqiao Chen & Meng Zhang & Yulin Xu & Xia Li & Ming Chen & Jiahui Lu & Pengxu Qian & He Huang, 2024. "Nlrc3 signaling is indispensable for hematopoietic stem cell emergence via Notch signaling in vertebrates," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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