CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.[1][2][3]
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.[4][5][6][7] 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.[8]
The CD34 protein is a member of a family of single-pass transmembrane sialomucin proteins that show expression on early hematopoietic and vascular-associated tissue.[9] However, little is known about its exact function.[10]
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.[11][12] 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.[13][14] Finally, recent data suggest CD34 may also play a more selective role in chemokine-dependent migration of eosinophils and dendritic cell precursors.[15][16] Regardless of its mode of action, under all circumstances CD34, and its relatives podocalyxin and endoglycan, facilitates cell migration.[9][15]
It is important to mention that Long-Term Hematopoietic Stem Cells (LT-HSCs) in mice and humans are the hematopoietic cells with the greatest self-renewal capacity.[citation needed] Human HSCs express the CD34 marker.[citation needed]
CD34 is expressed in roughly 20% of murine hematopoietic stem cells,[17] and can be stimulated and reversed.[18]
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 multipotential hemopoietic 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,[19] liver cirrhosis[20] and peripheral vascular disease.[21]
↑Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG (Apr 1992). "Structure of the gene encoding CD34, a human hematopoietic stem cell antigen". Genomics. 12 (4): 788–94. doi:10.1016/0888-7543(92)90310-O. PMID1374051.
↑Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH (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): 157–65. PMID6586833.
↑Tindle RW. Nichols R. Chan L. Campana D. Birnie GD. (1985). "A novel monoclonal antibody BI-3C5 recognises myeloblasts and non-B, non-T lymphoblasts in acute leukaemia and CGL blast crises, and react with immature cells in normal bone marrow". Leukemia Research. 9: 1–9. doi:10.1016/0145-2126(85)90016-5.
↑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.
↑ 9.09.1Nielsen JS, McNagny KM (Nov 2008). "Novel functions of the CD34 family". Journal of Cell Science. 121 (Pt 22): 3683–92. doi:10.1242/jcs.037507. PMID18987355.
↑Furness SG, McNagny K (2006). "Beyond mere markers: functions for CD34 family of sialomucins in hematopoiesis". Immunologic Research. 34 (1): 13–32. doi:10.1385/IR:34:1:13. PMID16720896.
↑Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J (Jul 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): 1499–509. doi:10.1111/j.1572-0241.2007.01189.x. PMID17459027.
↑Drew E, Merzaban JS, Seo W, Ziltener HJ, McNagny KM (Jan 2005). "CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution". Immunity. 22 (1): 43–57. doi:10.1016/j.immuni.2004.11.014. PMID15664158.
↑Strilić B, Kucera T, Eglinger J, Hughes MR, McNagny KM, Tsukita S, Dejana E, Ferrara N, Lammert E (Oct 2009). "The molecular basis of vascular lumen formation in the developing mouse aorta". Developmental Cell. 17 (4): 505–15. doi:10.1016/j.devcel.2009.08.011. PMID19853564.
↑Ogawa M, Tajima F, Ito T, Sato T, Laver JH, Deguchi T (Jun 2001). "CD34 expression by murine hematopoietic stem cells. Developmental changes and kinetic alterations". Annals of the New York Academy of Sciences. 938: 139–45. Bibcode:2001NYASA.938..139O. doi:10.1111/j.1749-6632.2001.tb03583.x. PMID11458501.
↑Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I (Oct 2006). "Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy". Stem Cells. 24 (10): 2292–8. doi:10.1634/stemcells.2005-0542. PMID16778155.
↑Subrammaniyan R, Amalorpavanathan J, Shankar R, Rajkumar M, Baskar S, Manjunath SR, Senthilkumar R, Murugan P, Srinivasan VR, Abraham S (Sep 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): 993–9. doi:10.3109/14653249.2011.579961. PMID21671823.
↑Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ (Jun 2001). "The adapter protein CrkL associates with CD34". Blood. 97 (12): 3768–75. doi:10.1182/blood.V97.12.3768. PMID11389015.
Bellini A, Mattoli S (Sep 2007). "The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses". Laboratory Investigation. 87 (9): 858–70. doi:10.1038/labinvest.3700654. PMID17607298.
Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG (Apr 1992). "Structure of the gene encoding CD34, a human hematopoietic stem cell antigen". Genomics. 12 (4): 788–94. doi:10.1016/0888-7543(92)90310-O. PMID1374051.
Sutherland DR, Watt SM, Dowden G, Karhi K, Baker MA, Greaves MF, Smart JE (Dec 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 (Feb 1993). "Two alternative forms of cDNA encoding CD34". Experimental Hematology. 21 (2): 236–42. PMID7678811. INIST:4784611.
Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M (Sep 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID8889549.
Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ (Jun 2001). "The adapter protein CrkL associates with CD34". Blood. 97 (12): 3768–75. doi:10.1182/blood.V97.12.3768. PMID11389015.
Dobo I, Robillard N, Pineau D, Geneviève F, Piard N, Rapp MJ, Boasson M, Zandecki M, Hermouet S (Nov 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): 639–46. doi:10.1007/s002770100365. PMID11757722.
Krauter J, Hartl M, Hambach L, Kohlenberg A, Gunsilius E, Ganser A, Heil G (Dec 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): 863–71. doi:10.1089/152581601317210953. PMID11798512.