Development of human lymphohematopoietic stem and progenitor cells definedby expression of CD34 and CD81

In this study, cord blood CD34(+) cells expressed CD81, a member of the tra nsmembrane 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 t hen examined by using suspension and clonogenic cultures for hematopoietic potential, coculture with MS-5 cells for B-cell potential, organ cultures o f thymus robes from nonobese diabetic/severe combined immunodeficiency dise ase (NOD/SCID) fetal mice, coculture with stromal cells derived from NOD/SC ID fetal-mouse liver tissue for natural killer (NK) cell and mast cell pote ntials, and xenotransplantation into NODI SCID mice for long-term repopulat ing (LTR) ability. CD34(+)CD81(+) cells represented a heterogeneous populat ion that had ail the lymphohematopoietic activities, including NOD/SCID mou se-repopulating ability. CD34(low)CD81(+) cells were enriched in erythroid, megakaryocytic, and NK lineage potentials but had lost T-cell and B-cell p otentials and LTR ability. The CD34(+)CD81(high) fraction was depleted of m ost lymphohematopoietic potentials except NK cell and mast cell potentials. Thus, along the differentiation cascade from CD34(+)CD81(+) lymphohematopo ietic stem cells, an up-regulation of CD81 or a down-regulation of CD34 res ults in a change in lymphohematopoietic properties. CD81 may serve as a mar ker for defining developmental stages of lymphohematopoietic stem cells. (C ) 2001 by The American Society of Hematology.