title: CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells.
abstract: In the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identified very primitive human cord blood (CB)-derived CD34- severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection method. In this study, we investigated the roles of the MPL expression in the human primitive HSC compartment. The SRC activities of the highly purified CB-derived 18Lin-CD34+/-MPL+/- cells were analyzed using NOG mice. In the primary recipient mice, nearly all mice that received CD34+/-MPL+/- cells were repopulated with human CD45+ cells. Nearly all of these mice that received CD34+MPL+/- and CD34-MPL- cells showed a secondary repopulation. Interestingly, the secondary recipient mice that received CD34+/-MPL- cells showed a distinct tertiary repopulation. These results clearly indicate that the CD34+/- SRCs not expressing MPL sustain a long-term (LT) (>1 year) human cell repopulation in NOG mice. Moreover, CD34- SRCs generate CD34+CD38-CD90+ SRCs in vitro and in vivo. These findings provide a new concept that CD34-MPL- SRCs reside at the apex of the human HSC hierarchy.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sumide
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamura
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Nakatsuka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujioka
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sonoda
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human