Development of human lymphohematopoietic stem and progenitor cells defined by expression of CD34 and CD81.
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(+), CD34(low)CD81(+), and CD34(+)CD81(high). 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. CD34(low)CD81(+) cells were enriched in erythroid, megakaryocytic, and NK lineage potentials but had lost T-cell and B-cell potentials and LTR ability. The CD34(+)CD81(high) 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. (Blood. 2001;97:3755-3762)
Ma
F
F
Divisions of Cellular Therapy and Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Wada
M
M
Yoshino
H
H
Ebihara
Y
Y
Ishii
T
T
Manabe
A
A
Tanaka
R
R
Maekawa
T
T
Ito
M
M
Mugishima
H
H
Asano
S
S
Nakahata
T
T
Tsuji
K
K
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D018952:Antigens, CD34 / Q000096:biosynthesis*; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology; D005333:Fetus / Q000166:cytology; D006410:Hematopoiesis / Q000276:immunology* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008565:Membrane Proteins; D051379:Mice; D016513:Mice, SCID; D017154:Stromal Cells; D060225:Tetraspanin 28; D014183:Transplantation, Heterologous
D015703:Antigens, CD; D018952:Antigens, CD34; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; D008565:Membrane Proteins; D060225:Tetraspanin 28