Development of human lymphohematopoietic stem and progenitor cells defined by expression of CD34 and CD81

Abstract

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. © 2001 by The American Society of Hematology.