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

Keisuke Sumide, Yoshikazu Matsuoka, Hiroshi Kawamura, Ryusuke Nakatsuka, Tatsuya Fujioka, Hiroaki Asano, Yoshihiro Takihara and Yoshiaki Sonoda ()
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Keisuke Sumide: Kansai Medical University
Yoshikazu Matsuoka: Kansai Medical University
Hiroshi Kawamura: Kansai Medical University
Ryusuke Nakatsuka: Kansai Medical University
Tatsuya Fujioka: Kansai Medical University
Hiroaki Asano: Kyoto Prefectural University of Medicine
Yoshihiro Takihara: Hiroshima University
Yoshiaki Sonoda: Kansai Medical University

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04441-z

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