CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.[5][6][7]
CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first described on hematopoietic stem cells independently by Civin et al. and Tindle et al.[8][9][10][11] as a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of hematopoietic stem cells to bone marrow extracellular matrix or directly to stromal cells. Clinically, it is associated with the selection and enrichment of hematopoietic stem cells for bone marrow transplants. Due to these historical and clinical associations, CD34 expression is almost ubiquitously related to hematopoietic cells; however, it is actually found on many other cell types as well.[12]
Function
The CD34 protein is a member of a family of single-pass transmembrane sialomucin proteins that show expression on early haematopoietic and vascular-associated progenitor cells.[13] However, little is known about its exact function.[14]
CD34 is also an important adhesion molecule and is required for T cells to enter lymph nodes. It is expressed on lymph node endothelia, whereas the L-selectin to which it binds is on the T cell.[15][16] Conversely, under other circumstances CD34 has been shown to act as molecular "Teflon" and block mast cell, eosinophil and dendritic cell precursor adhesion, and to facilitate opening of vascular lumina.[17][18] Finally, recent data suggest CD34 may also play a more selective role in chemokine-dependent migration of eosinophils and dendritic cell precursors.[19][20] Regardless of its mode of action, under all circumstances CD34, and its relatives podocalyxin and endoglycan, facilitates cell migration.[13][19]
Tissue distribution
CD34 is expressed in hematopoietic progenitor cells and endothelial cells of blood vessels. Thus, it has been used as a marker for capillaries and blood vessels. One of the most densely vascular organs is the kidney, wherein networks of capillaries are intertwined with renal tubules. In kidney sections, these networks of capillaries have been visualized by confocal microscopy of fluorescently labelled anti-CD34 antibodies.[21] The presence of CD34 on non-hematopoietic cells in various tissues has been linked to progenitor and adult stem cell phenotypes.[12]
It is important to mention that Long-Term Haematopoietic Stem Cells (LT-HSCs) in mice and humans are the haematopoietic cells with the greatest self-renewal capacity and were shown to be CD34+ and CD38− cell fraction within the lineage-depleted cell population (LIn−).[22][23] Human HSCs express the CD34 marker.[22][24] Later studies have reported that low rhodamine retention identifies LT-HSCs within the Lin−CD34+CD38− population.[25][26][27]
CD34 is expressed in roughly 20% of murine haematopoietic stem cells,[28] and can be stimulated and reversed.[29]
Clinical applications
CD34+ is often used clinically to quantify the number of haemopoietic stem cells for use in haemopoietic stem cell transplantation. This is generally a useful marker for cell dosing although there is some evidence that the CD34+ quantification may not be reliable in some circumstances.[30] CD34+ cells may be isolated from blood samples using immunomagnetic techniques and used for CD34+ transplants, which have lower rates of graft-versus-host disease.[31]
Antibodies are used to quantify and purify hematopoieticprogenitor stem cells for research and for clinical bone marrow transplantation. However, counting CD34+ mononuclear cells may overestimate myeloid blasts in bone marrow smears due to hematogones (B lymphocyte precursors) and CD34+ megakaryocytes.
Cells observed as CD34+ and CD38- are of an undifferentiated, primitive form; i.e., they are multipotent hematopoietic stem cells. Thus, because of their CD34+ expression, such undifferentiated cells can be sorted out.
Injection of CD34+ hematopoietic stem cells has been clinically applied to treat various diseases including spinal cord injury,[32] liver cirrhosis[33] and peripheral vascular disease.[34]
Interactions
CD34 has been shown to interact with CRKL.[35] It also interacts with L-selectin, important in inflammation. CD34- has been related to hair follicles' melanocyte regeneration and CD34+ with neuronal regeneration.
^Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG (April 1992). "Structure of the gene encoding CD34, a human hematopoietic stem cell antigen". Genomics. 12 (4): 788–794. doi:10.1016/0888-7543(92)90310-O. PMID1374051.
^Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH (July 1984). "Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells". Journal of Immunology. 133 (1): 157–165. doi:10.4049/jimmunol.133.1.157. PMID6586833.
^Tindle RW, Nichols RA, Chan L, Campana D, Catovsky D, Birnie GD (1985). "A novel monoclonal antibody BI-3C5 recognises myeloblasts and non-B non-T lymphoblasts in acute leukaemias and CGL blast crises, and reacts with immature cells in normal bone marrow". Leukemia Research. 9 (1): 1–9. doi:10.1016/0145-2126(85)90016-5. PMID3857402.
^Tindle RW. Katz F. Martin H. Watt D. Catovsky D. Janossy G. Greaves M. (1987). "BI-3C5 (CD34) defines multipotential and lineage restricted progenitor cells and their leukaemic counterparts ". In 'Leucocyte Typing 111: White Cell Differentiation Antigens. Oxford University Press, 654-655.
^Loken M. Shah V. Civin CI.. (1987). "Characterization of myeloid antigens on human bone marrow using multicolour immunofluorescence". In: McMichael, Leucocyte Typing III:White Cell Differentiation Antigens.Oxford University Press 630-635.
^Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, et al. (July 2007). "Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis". The American Journal of Gastroenterology. 102 (7): 1499–1509. doi:10.1111/j.1572-0241.2007.01189.x. PMID17459027. S2CID7630223.
^Kumaran GK, Hanukoglu I (2024). "Mapping the cytoskeletal architecture of renal tubules and surrounding peritubular capillaries in the kidney". Cytoskeleton (Hoboken). 81 (4–5): 227–237. doi:10.1002/cm.21809. PMID37937511.
^ abRamsfjell V, Bryder D, Björgvinsdóttir H, Kornfält S, Nilsson L, Borge OJ, Jacobsen SE (December 1999). "Distinct requirements for optimal growth and In vitro expansion of human CD34(+)CD38(-) bone marrow long-term culture-initiating cells (LTC-IC), extended LTC-IC, and murine in vivo long-term reconstituting stem cells". Blood. 94 (12): 4093–4102. doi:10.1182/blood.V94.12.4093. PMID10590054.
^Wolf NS, Koné A, Priestley GV, Bartelmez SH (May 1993). "In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342-rhodamine 123 FACS selection". Experimental Hematology. 21 (5): 614–622. PMID8513861.
^Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, et al. (October 2006). "Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy". Stem Cells. 24 (10): 2292–2298. doi:10.1634/stemcells.2005-0542. PMID16778155. S2CID5649484.
^Subrammaniyan R, Amalorpavanathan J, Shankar R, Rajkumar M, Baskar S, Manjunath SR, et al. (September 2011). "Application of autologous bone marrow mononuclear cells in six patients with advanced chronic critical limb ischemia as a result of diabetes: our experience". Cytotherapy. 13 (8): 993–999. doi:10.3109/14653249.2011.579961. PMID21671823. S2CID27251276.
Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG (April 1992). "Structure of the gene encoding CD34, a human hematopoietic stem cell antigen". Genomics. 12 (4): 788–794. doi:10.1016/0888-7543(92)90310-O. PMID1374051.
Sutherland DR, Watt SM, Dowden G, Karhi K, Baker MA, Greaves MF, Smart JE (December 1988). "Structural and partial amino acid sequence analysis of the human hemopoietic progenitor cell antigen CD34". Leukemia. 2 (12): 793–803. PMID2462139.
Nakamura Y, Komano H, Nakauchi H (February 1993). "Two alternative forms of cDNA encoding CD34". Experimental Hematology. 21 (2): 236–242. PMID7678811. INIST4784611.
Dobo I, Robillard N, Pineau D, Geneviève F, Piard N, Rapp MJ, et al. (November 2001). "Use of pathology-specific peripheral blood CD34 thresholds to predict leukapheresis CD34 content with optimal accuracy: a bicentric analysis of 299 leukaphereses". Annals of Hematology. 80 (11): 639–646. doi:10.1007/s002770100365. PMID11757722. S2CID23018429.
Krauter J, Hartl M, Hambach L, Kohlenberg A, Gunsilius E, Ganser A, Heil G (December 2001). "Receptor-mediated endocytosis of CD34 on hematopoietic cells after stimulation with the monoclonal antibody anti-HPCA-1". Journal of Hematotherapy & Stem Cell Research. 10 (6): 863–871. doi:10.1089/152581601317210953. PMID11798512.
