Long-Term Lymphohematopoietic Reconstitution by a Single CD34-Low/Negative Hematopoietic Stem Cell

Hematopoietic stem cells (HSCs) supply all blood cells throughout life by making use of their self-renewal and multilineage differentiation capabilities. A monoclonal antibody raised to the mouse homolog of CD34 (mCD34) was used to purify mouse HSCs to near homogeneity. Unlike in humans, primitive adult mouse bone marrow HSCs were detected in the mCD34 low to negative fraction. Injection of a single mCD34lo/−, c-Kit+, Sca-1+, lineage markers negative (Lin−) cell resulted in long-term reconstitution of the lymphohematopoietic system in 21 percent of recipients. Thus, the purified HSC population should enable analysis of the self-renewal and multilineage differentiation of individual HSCs.

[1]  I. Weissman,et al.  Clonal analysis of hematopoietic stem-cell differentiation in vivo. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[2]  T. Suda,et al.  Two types of murine CD34 mRNA generated by alternative splicing. , 1992, Blood.

[3]  M. Fackler,et al.  Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. , 1984, Journal of immunology.

[4]  M. Fackler,et al.  Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells. , 1994, Blood.

[5]  M. Greaves,et al.  The gene encoding the stem cell antigen, CD34, is conserved in mouse and expressed in haemopoietic progenitor cell lines, brain, and embryonic fibroblasts. , 1991, International immunology.

[6]  S. Nishikawa,et al.  Sequential analysis of hematopoietic reconstitution achieved by transplantation of hematopoietic stem cells. , 1993, Blood.

[7]  H. Broxmeyer,et al.  Hematopoietic defects in mice lacking the sialomucin CD34. , 1996, Blood.

[8]  H. Nakauchi,et al.  CD4dull+ hematopoietic progenitor cells in murine bone marrow , 1993 .

[9]  B. Torbett,et al.  CD4 is expressed on murine pluripotent hematopoietic stem cells. , 1992, Blood.

[10]  H. Nakauchi,et al.  In vivo self-renewal of c-Kit+ Sca-1+ Lin(low/-) hemopoietic stem cells. , 1996, Journal of immunology.

[11]  S. Nishikawa,et al.  In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells. , 1992, Blood.

[12]  K. Cornetta,et al.  Persistence of human multilineage, self-renewing lymphohematopoietic stem cells in chimeric sheep. , 1993, Blood.

[13]  K. Weinberg,et al.  Engraftment of gene–modified umbilical cord blood cells in neonates with adenosine deaminase deficiency , 1995, Nature Medicine.

[14]  J. Wagner,et al.  Separation of pluripotent haematopoietic stem cells from spleen colony-forming cells , 1990, Nature.

[15]  Kozo Kaibuchi,et al.  Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase) , 1996, Science.

[16]  W. Friedrich,et al.  Evidence for engraftment of donor-type multipotent CD34+ cells in a patient with selective T-lymphocyte reconstitution after bone marrow transplantation for B-SCID , 1994 .

[17]  I. Weissman,et al.  Isolation of a candidate human hematopoietic stem-cell population. , 1992, Proceedings of the National Academy of Sciences of the United States of America.