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CD34
Identifiers
Aliases	CD34, entrez:947, CD34 molecule
External IDs	OMIM: 142230; MGI: 88329; HomoloGene: 1343; GeneCards: CD34; OMA:CD34 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1q32.2 Start 207,880,972 bp End 207,911,402 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1 H6|1 98.38 cM Start 194,621,127 bp End 194,643,587 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart right auricle gastric mucosa subcutaneous adipose tissue Descending thoracic aorta left uterine tube right lobe of thyroid gland tibial nerve body of uterus right coronary artery Top expressed in vasculature of trunk efferent ductule ankle lip left lung lobe uterus carotid body dermis cervix skin of abdomen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transcription factor binding sulfate binding carbohydrate binding Cellular component cytoplasm integral component of membrane membrane plasma membrane integral component of plasma membrane extracellular region cell surface basal plasma membrane glomerular endothelium fenestra apical plasma membrane intercellular bridge perinuclear region of cytoplasm lysosome external side of plasma membrane cell periphery Biological process extracellular exosome assembly stem cell proliferation positive regulation of interleukin-10 production cell motility negative regulation of blood coagulation metanephric glomerular mesangial cell differentiation paracrine signaling hematopoietic stem cell proliferation positive regulation of granulocyte colony-stimulating factor production negative regulation of gene expression positive regulation of angiogenesis regulation of blood pressure vascular wound healing positive regulation of gene expression glomerular filtration negative regulation of nitric oxide biosynthetic process cell adhesion endothelial cell proliferation mesangial cell-matrix adhesion tissue homeostasis positive regulation of vasculogenesis endothelium development regulation of immune response negative regulation of cellular response to heat positive regulation of transforming growth factor beta production glomerular endothelium development negative regulation of tumor necrosis factor production cell-matrix adhesion cell population proliferation positive regulation of odontogenesis negative regulation of cellular response to hypoxia leukocyte migration signal transduction transdifferentiation negative regulation of neuron death cell-cell adhesion hemopoiesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 947 12490 Ensembl ENSG00000174059 ENSMUSG00000016494 UniProt P28906 Q64314 RefSeq (mRNA) NM_001025109 NM_001773 NM_001111059 NM_133654 RefSeq (protein) NP_001020280 NP_001764 NP_001104529 NP_598415 Location (UCSC) Chr 1: 207.88 – 207.91 Mb Chr 1: 194.62 – 194.64 Mb PubMed search
Wikidata
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CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.

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. 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.

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. However, little is known about its exact function.

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. 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. Finally, recent data suggest CD34 may also play a more selective role in chemokine-dependent migration of eosinophils and dendritic cell precursors. Regardless of its mode of action, under all circumstances CD34, and its relatives podocalyxin and endoglycan, facilitates cell migration.

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. The presence of CD34 on non-hematopoietic cells in various tissues has been linked to progenitor and adult stem cell phenotypes.

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). Human HSCs express the CD34 marker. Later studies have reported that low rhodamine retention identifies LT-HSCs within the LinCD34CD38 population.

CD34 is expressed in roughly 20% of murine haematopoietic stem cells, and can be stimulated and reversed.

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. 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.

Antibodies are used to quantify and purify hematopoietic progenitor 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.

In tumors, CD34 is found in alveolar soft part sarcoma, preB-ALL (positive in 75%), AML (40%), AML-M7 (most), dermatofibrosarcoma protuberans, gastrointestinal stromal tumors, giant cell fibroblastoma, granulocytic sarcoma, Kaposi’s sarcoma, liposarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumors, meningeal hemangiopericytomas, meningiomas, neurofibromas, schwannomas, and papillary thyroid carcinoma.

A negative CD34 may exclude Ewing's sarcoma/PNET, myofibrosarcoma of the breast, and inflammatory myofibroblastic tumors of the stomach.

Injection of CD34+ hematopoietic stem cells has been clinically applied to treat various diseases including spinal cord injury, liver cirrhosis and peripheral vascular disease.

Interactions

CD34 has been shown to interact with CRKL. It also interacts with L-selectin, important in inflammation. CD34- has been related to hair follicles' melanocyte regeneration and CD34+ with neuronal regeneration.

See also

• Cluster of differentiation
• List of histologic stains that aid in diagnosis of cutaneous conditions

References

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7. 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. PMID 1374051.
8. 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. PMID 6586833.
9. 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. PMID 3857402.
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23. Hogan CJ, Shpall EJ, Keller G (January 2002). "Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice". Proceedings of the National Academy of Sciences of the United States of America. 99 (1): 413–418. Bibcode:2002PNAS...99..413H. doi:10.1073/pnas.012336799. PMC 117574. PMID 11782553.
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25. McKenzie JL, Takenaka K, Gan OI, Doedens M, Dick JE (January 2007). "Low rhodamine 123 retention identifies long-term human hematopoietic stem cells within the Lin-CD34+CD38- population". Blood. 109 (2): 543–545. doi:10.1182/blood-2006-06-030270. PMID 16990597. S2CID 25804835.
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34. 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. PMID 21671823. S2CID 27251276.
35. Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ (June 2001). "The adapter protein CrkL associates with CD34". Blood. 97 (12): 3768–3775. doi:10.1182/blood.V97.12.3768. PMID 11389015.

Further reading

• Bellini A, Mattoli S (September 2007). "The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses". Laboratory Investigation; A Journal of Technical Methods and Pathology. 87 (9): 858–870. doi:10.1038/labinvest.3700654. PMID 17607298.
• Simmons DL, Satterthwaite AB, Tenen DG, Seed B (January 1992). "Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells". Journal of Immunology. 148 (1): 267–271. doi:10.4049/jimmunol.148.1.267. PMID 1370171.
• 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. PMID 1374051.
• Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, et al. (June 1990). "Expression of the CD34 gene in vascular endothelial cells". Blood. 75 (12): 2417–2426. doi:10.1182/blood.V75.12.2417.2417. PMID 1693532.
• Fackler MJ, Civin CI, Sutherland DR, Baker MA, May WS (July 1990). "Activated protein kinase C directly phosphorylates the CD34 antigen on hematopoietic cells". The Journal of Biological Chemistry. 265 (19): 11056–11061. doi:10.1016/S0021-9258(19)38556-4. PMID 1694174.
• 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. PMID 2462139.
• Nakamura Y, Komano H, Nakauchi H (February 1993). "Two alternative forms of cDNA encoding CD34". Experimental Hematology. 21 (2): 236–242. PMID 7678811. INIST 4784611.
• Huyhn A, Dommergues M, Izac B, Croisille L, Katz A, Vainchenker W, Coulombel L (December 1995). "Characterization of hematopoietic progenitors from human yolk sacs and embryos". Blood. 86 (12): 4474–4485. doi:10.1182/blood.V86.12.4474.bloodjournal86124474. PMID 8541536.
• Tavian M, Coulombel L, Luton D, Clemente HS, Dieterlen-Lièvre F, Péault B (January 1996). "Aorta-associated CD34+ hematopoietic cells in the early human embryo". Blood. 87 (1): 67–72. doi:10.1182/blood.V87.1.67.67. PMID 8547678.
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, et al. (September 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–828. doi:10.1101/gr.6.9.807. PMID 8889549.
• Uchida N, Yang Z, Combs J, Pourquié O, Nguyen M, Ramanathan R, et al. (April 1997). "The characterization, molecular cloning, and expression of a novel hematopoietic cell antigen from CD34+ human bone marrow cells". Blood. 89 (8): 2706–2716. doi:10.1182/blood.V89.8.2706. PMID 9108388.
• Ruiz ME, Cicala C, Arthos J, Kinter A, Catanzaro AT, Adelsberger J, et al. (October 1998). "Peripheral blood-derived CD34+ progenitor cells: CXC chemokine receptor 4 and CC chemokine receptor 5 expression and infection by HIV". Journal of Immunology. 161 (8): 4169–4176. doi:10.4049/jimmunol.161.8.4169. PMID 9780190.
• Kees UR, Ford J (February 1999). "Synergistic action of stem-cell factor and interleukin-7 in a human immature T-cell line". Immunology. 96 (2): 202–206. doi:10.1046/j.1365-2567.1999.00674.x. PMC 2326741. PMID 10233696.
• Bistrup A, Bhakta S, Lee JK, Belov YY, Gunn MD, Zuo FR, et al. (May 1999). "Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin". The Journal of Cell Biology. 145 (4): 899–910. doi:10.1083/jcb.145.4.899. PMC 2133194. PMID 10330415.
• Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, Le Bousse-Kerdilès MC (February 2000). "Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival". Blood. 95 (3): 756–768. doi:10.1182/blood.V95.3.756. PMID 10648383.
• Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ (June 2001). "The adapter protein CrkL associates with CD34". Blood. 97 (12): 3768–3775. doi:10.1182/blood.V97.12.3768. PMID 11389015.
• 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. PMID 11757722. S2CID 23018429.
• Hogan CJ, Shpall EJ, Keller G (January 2002). "Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice". Proceedings of the National Academy of Sciences of the United States of America. 99 (1): 413–418. Bibcode:2002PNAS...99..413H. doi:10.1073/pnas.012336799. JSTOR 3057551. PMC 117574. PMID 11782553. INIST 13429907.
• 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. PMID 11798512.
• Okuno Y, Iwasaki H, Huettner CS, Radomska HS, Gonzalez DA, Tenen DG, Akashi K (April 2002). "Differential regulation of the human and murine CD34 genes in hematopoietic stem cells". Proceedings of the National Academy of Sciences of the United States of America. 99 (9): 6246–6251. Bibcode:2002PNAS...99.6246O. doi:10.1073/pnas.092027799. JSTOR 3058657. PMC 122934. PMID 11983914.
• Hotfilder M, Röttgers S, Rosemann A, Jürgens H, Harbott J, Vormoor J (July 2002). "Immature CD34+CD19- progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal". Blood. 100 (2): 640–646. doi:10.1182/blood.V100.2.640. PMID 12091359.

External links

• Antigens,+CD34 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Mouse CD Antigen Chart
• Human CD Antigen Chart
• Human CD34 genome location and CD34 gene details page in the UCSC Genome Browser.

• Genes on human chromosome 1
• Clusters of differentiation
• Cell adhesion molecules