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A revised road map for the commitment of human cord blood CD34-negative hematopoietic stem cells

Author

Listed:
  • Keisuke Sumide

    (Kansai Medical University)

  • Yoshikazu Matsuoka

    (Kansai Medical University)

  • Hiroshi Kawamura

    (Kansai Medical University
    Kansai Medical University)

  • Ryusuke Nakatsuka

    (Kansai Medical University)

  • Tatsuya Fujioka

    (Kansai Medical University)

  • Hiroaki Asano

    (Kyoto Prefectural University of Medicine)

  • Yoshihiro Takihara

    (Hiroshima University
    Japanese Red Cross Osaka Blood Center)

  • Yoshiaki Sonoda

    (Kansai Medical University)

Abstract

We previously identified CD34-negative (CD34−) severe combined immunodeficiency (SCID)-repopulating cells as primitive hematopoietic stem cells (HSCs) in human cord blood. In this study, we develop a prospective ultra-high-resolution purification method by applying two positive markers, CD133 and GPI-80. Using this method, we succeed in purifying single long-term repopulating CD34− HSCs with self-renewing capability residing at the apex of the human HSC hierarchy from cord blood, as evidenced by a single-cell-initiated serial transplantation analysis. The gene expression profiles of individual CD34+ and CD34− HSCs and a global gene expression analysis demonstrate the unique molecular signature of CD34− HSCs. We find that the purified CD34− HSCs show a potent megakaryocyte/erythrocyte differentiation potential in vitro and in vivo. Megakaryocyte/erythrocyte progenitors may thus be generated directly via a bypass route from the CD34− HSCs. Based on these data, we propose a revised road map for the commitment of human CD34− HSCs in cord blood.

Suggested Citation

  • Keisuke Sumide & Yoshikazu Matsuoka & Hiroshi Kawamura & Ryusuke Nakatsuka & Tatsuya Fujioka & Hiroaki Asano & Yoshihiro Takihara & Yoshiaki Sonoda, 2018. "A revised road map for the commitment of human cord blood CD34-negative hematopoietic stem cells," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04441-z
    DOI: 10.1038/s41467-018-04441-z
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    Cited by:

    1. Kim Vanuytsel & Carlos Villacorta-Martin & Jonathan Lindstrom-Vautrin & Zhe Wang & Wilfredo F. Garcia-Beltran & Vladimir Vrbanac & Dylan Parsons & Evan C. Lam & Taylor M. Matte & Todd W. Dowrey & Sara, 2022. "Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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