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Blood, 15 June 2001, Vol. 97, No. 12, pp. 3755-3762
HEMATOPOIESIS
Development of human lymphohematopoietic stem and progenitor
cells defined by expression of CD34 and CD81
Feng Ma,
Mika Wada,
Hiroshi Yoshino,
Yasuhiro Ebihara,
Takefumi Ishii,
Atsushi Manabe,
Ryuhei Tanaka,
Taira Maekawa,
Mamoru Ito,
Hideo Mugishima,
Shigetaka Asano,
Tatsutoshi Nakahata, and
Kohichiro Tsuji
From the Divisions of Cellular Therapy and Molecular
Therapy, Advanced Clinical Research Center, and the Department of
Transfusion Medicine, Institute of Medical Science, University of
Tokyo, Tokyo, Japan; the Central Institute for Experimental Animals,
Kawasaki, Japan; the Department of Pediatrics, Nihon University School
of Medicine, Tokyo, Japan; and the Department of Pediatrics, Kyoto
University, Kyoto, Japan.
In this study, cord blood CD34+ cells expressed CD81, a
member of the transmembrane 4 superfamily, and were classified into 3 subpopulations on the basis of their expression levels:
CD34+CD81+,
CD34lowCD81+, and
CD34+CD81high. The lymphohematopoietic activity
of each subpopulation was then examined by using suspension and
clonogenic cultures for hematopoietic potential, coculture with MS-5
cells for B-cell potential, organ cultures of thymus lobes from
nonobese diabetic/severe combined immunodeficiency disease (NOD/SCID)
fetal mice, coculture with stromal cells derived from NOD/SCID
fetal-mouse liver tissue for natural killer (NK) cell and mast cell
potentials, and xenotransplantation into NOD/SCID mice for long-term
repopulating (LTR) ability. CD34+CD81+ cells
represented a heterogeneous population that had all the lymphohematopoietic activities, including NOD/SCID mouse-repopulating ability. CD34lowCD81+ cells were enriched in
erythroid, megakaryocytic, and NK lineage potentials but had lost
T-cell and B-cell potentials and LTR ability. The
CD34+CD81high fraction was depleted of most
lymphohematopoietic potentials except NK cell and mast cell potentials.
Thus, along the differentiation cascade from
CD34+CD81+ lymphohematopoietic stem cells, an
up-regulation of CD81 or a down-regulation of CD34 results in a change
in lymphohematopoietic properties. CD81 may serve as a marker for
defining developmental stages of lymphohematopoietic stem cells.
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