Alternative titles; symbols
HGNC Approved Gene Symbol: CD34
Cytogenetic location: 1q32.2 Genomic coordinates (GRCh38): 1:207,880,972-207,911,125 (from NCBI)
CD34 is a monomeric cell surface antigen with a molecular mass of approximately 110 kD that is selectively expressed on human hematopoietic progenitor cells.
Sutherland et al. (1988) performed partial amino acid analysis of highly purified CD34 antigen and found no significant sequence similarity with any previously described structures. Sequential immunoprecipitation and Western blot analysis indicated that this antigen is not a member of the leukosialin/sialophorin family, despite the fact that these molecules share several structural similarities.
Simmons et al. (1992) isolated a cDNA clone for CD34. They stated that the gene is expressed by small vessel endothelial cells in addition to hematopoietic progenitor cells and is a sialomucin of as-yet-unknown function.
Study of the CD34 cDNA permitted He et al. (1992) to demonstrate that it encodes a type I transmembrane protein with no obvious homology to other known proteins.
Sutherland et al. (1993) provided a review, including potential clinical applications in selecting for hematopoietic stem cell progenitors from tumor-contaminated marrow in preparation for transplantation and for genetic manipulation in gene therapy.
Satterthwaite et al. (1992) reported that the CD34 gene spans 26 kb and has 8 exons. Using RNase protection, they demonstrated that the start site of CD34 transcription is 258 bp upstream of the translational start site. He et al. (1992) showed that the upstream regulatory sequences of CD34 contain no TATA or CAAT box sequences, but MYB, MYC, and ETS-like binding motifs were identified.
Continuous turnover of epithelia is ensured by the extensive self-renewal capacity of tissue-specific stem cells. Similarly, epithelial tumor maintenance relies on cancer stem cells, which co-opt stem cell properties. In murine skin, follicular morphogenesis is driven by bulge stem cells that specifically express CD34. Malanchi et al. (2008) identified a population of cells in early epidermal tumors characterized by phenotype and functional similarities to normal bulge skin stem cells. This population contains cancer stem cells, which are the only cells with tumor initiation properties. Transplants derived from these cancer stem cells preserve the hierarchical organization of the primary tumor. Malanchi et al. (2008) described beta-catenin (116806) signaling as being essential in sustaining the cancer stem cell phenotype. Ablation of the beta-catenin gene results in the loss of cancer stem cells and complete tumor regression. In addition, Malanchi et al. (2008) provided evidence for the involvement of increased beta-catenin signaling in malignant human squamous cell carcinomas. Malanchi et al. (2008) concluded that because Wnt/beta-catenin signaling is not essential for normal epidermal homeostasis, such a mechanistic difference may thus be targeted to eliminate cancer stem cells and consequently eradicate squamous cell carcinomas.
By Southern blot analysis of DNA from a panel of human/mouse somatic cell hybrids using a CD34 cDNA probe, Tenen et al. (1990) demonstrated that the gene for CD34 is located on 1q12-qter. By means of in situ hybridization, Howell et al. (1991) narrowed the assignment to 1q32. By fluorescence in situ hybridization, Satterthwaite et al. (1992) mapped the gene to 1q32.
To analyze the involvement of CD34 in hematopoiesis, Cheng et al. (1996) produced both embryonic stem (ES) cells in mice null for the expression of this mucin. Analysis of yolk sac-like hematopoietic development in embryoid bodies derived from CD34-null ES cells showed a significant delay in both erythroid and myeloid differentiation that could be reversed by transfection of the mutant ES cells with CD34 constructs expressing either a complete or truncated cytoplasmic domain. In spite of these diminished embryonic hematopoietic progenitor numbers, the CD34-null mice developed normally, and the hematopoietic profile of adult blood appeared typical. However, the colony-forming activity of hematopoietic progenitors derived from both bone marrow and spleen was significantly reduced in adult CD34-deficient animals.
Hematopoietic stem cells (HSCs) give rise to all blood cells. CD34 is a sialomucin-like adhesion molecule that is expressed on a few percent of primitive bone marrow cells. In human bone marrow, virtually all colony-forming unit activity resides in the population expressing human CD34. In primates, CD34-positive cells, but not CD34-negative cells, repopulate lethally irradiated baboons. On the other hand, in murine hematopoiesis, HSCs are found almost exclusively in the CD34-negative to -low fraction. Okuno et al. (2002) made transgenic mouse strains with human genomic P1 artificial chromosome clones spanning the entire CD34 genomic locus. In all transgenic mouse strains, a vast majority of phenotypic and functional HSC populations including mouse CD34-negative or -low cells expressed the human CD34 transgene. These data strongly supported the notion that CD34-positive human bone marrow cells contain long-term HSCs that can maintain hematopoiesis throughout life.
Using fluorescence intravital microscopy (IVM) with homing assays, Hidalgo et al. (2002) examined the repopulation of bone marrow of sublethally irradiated nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice, which have multiple defects in innate and adaptive immunologic functions, with human CD34-positive hematopoietic progenitor cells obtained either from cord blood or from adult bone marrow or peripheral blood. Human hematopoietic progenitor cells rolled and arrested in NOD/SCID bone marrow microvessels, and the rolling capacity of neonatal cord blood cells was much lower than that of adult cells. Rolling and retention were nearly abolished in NOD/SCID Selp (173610) -/- Sele (131210) -/- mice and in NOD/SCID Sele -/- mice. Flow cytometric and IVM analyses suggested that the neonatal defect resulted from expression of a nonfunctional form of SELPLG (600738) on cord blood CD34-positive cells that were unable to bind Selp. This subset of cells was enriched in CD34-positive/CD38 (107270)-low/negative progenitors. Hidalgo et al. (2002) proposed that manipulation of expression of selectins and their ligands may improve homing of cord blood CD34-positive cells to bone marrow.
Cheng, J., Baumhueter, S., Cacalano, G., Carver-Moore, K., Thibodeaux, H., Thomas, R., Broxmeyer, H. E., Cooper, S., Hague, N., Moore, M., Lasky, L. A. Hematopoietic defects in mice lacking the sialomucin CD34. Blood 87: 479-490, 1996. [PubMed: 8555469]
He, X.-Y., Antao, V. P., Basila, D., Marx, J. C., Davis, B. R. Isolation and molecular characterization of the human CD34 gene. Blood 79: 2296-2302, 1992. [PubMed: 1373971]
Hidalgo, A., Weiss, L. A., Frenette, P. S. Functional selectin ligands mediating human CD34+ cell interactions with bone marrow endothelium are enhanced postnatally. J. Clin. Invest. 110: 559-569, 2002. [PubMed: 12189250] [Full Text: https://doi.org/10.1172/JCI14047]
Howell, S. M., Molgaard, H. V., Greaves, M. F., Spurr, N. K. Localisation of the gene coding for the haemopoietic stem cell antigen CD34 to chromosome 1q32. Hum. Genet. 87: 625-627, 1991. [PubMed: 1717362] [Full Text: https://doi.org/10.1007/BF00209027]
Malanchi, I., Peinado, H., Kassen, D., Hussenet, T., Metzger, D., Chambon, P., Huber, M., Hohl, D., Cano, A., Birchmeier, W., Huelsken, J. Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nature 452: 650-653, 2008. [PubMed: 18385740] [Full Text: https://doi.org/10.1038/nature06835]
Okuno, Y., Iwasaki, H., Huettner, C. S., Radomska, H. S., Gonzalez, D. A., Tenen, D. G., Akashi, K. Differential regulation of the human and murine CD34 genes in hematopoietic stem cells. Proc. Nat. Acad. Sci. 99: 6246-6251, 2002. [PubMed: 11983914] [Full Text: https://doi.org/10.1073/pnas.092027799]
Satterthwaite, A. B., Burn, T. C., Le Beau, M. M., Tenen, D. G. Structure of the gene encoding CD34, a human hematopoietic stem cell antigen. Genomics 12: 788-794, 1992. [PubMed: 1374051] [Full Text: https://doi.org/10.1016/0888-7543(92)90310-o]
Simmons, D. L., Satterthwaite, A. B., Tenen, D. G., Seed, B. Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells. J. Immun. 148: 267-271, 1992. [PubMed: 1370171]
Sutherland, D. R., Stewart, A. K., Keating, A. CD34 antigen: molecular features and potential clinical applications. Stem Cells 11 (suppl. 3): 50-57, 1993. [PubMed: 7507757] [Full Text: https://doi.org/10.1002/stem.5530110914]
Sutherland, D. R., Watt, S. M., Dowden, G., Karhi, K., Baker, M. A., Greaves, M. F., Smart, J. E. Structural and partial amino acid sequence analysis of the human hemopoietic progenitor cell antigen CD34. Leukemia 2: 793-803, 1988. [PubMed: 2462139]
Tenen, D. G., Satterthwaite, A. B., Borson, R., Simmons, D., Eddy, R. L., Shows, T. B. Chromosome 1 localization of the gene for CD34, a surface antigen of human stem cells. Cytogenet. Cell Genet. 53: 55-57, 1990. [PubMed: 1691071] [Full Text: https://doi.org/10.1159/000132894]