CD34

CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.[5][6][7]

CD34
Identifiers
AliasesCD34, entrez:947, CD34 molecule
External IDsOMIM: 142230 MGI: 88329 HomoloGene: 1343 GeneCards: CD34
Orthologs
SpeciesHumanMouse
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 MbChr 1: 194.62 – 194.64 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Cells expressing CD34 (CD34+ cell) are normally found in the umbilical cord and bone marrow as haematopoietic cells, or in endothelial progenitor cells, endothelial cells of blood vessels but not lymphatics (except pleural lymphatics), mast cells, a sub-population of dendritic cells (which are factor XIIIa-negative) in the interstitium and around the adnexa of dermis of skin, as well as cells in soft tissue tumors like DFSP, GIST, SFT, HPC, and to some degree in MPNSTs, etc. 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−).[21][22] Human HSCs express the CD34 marker.[21][23] Later studies have reported that low rhodamine retention identifies LT-HSCs within the Lin−CD34+CD38− population.[24][25][26]

CD34 is expressed in roughly 20% of murine haematopoietic stem cells,[27] and can be stimulated and reversed.[28]

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.[29] 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.[30]

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,[31] liver cirrhosis[32] and peripheral vascular disease.[33]

Interactions

CD34 has been shown to interact with CRKL.[34] 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

References
  1. GRCh38: Ensembl release 89: ENSG00000174059 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000016494 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: CD34 CD34 molecule".
  6. 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. PMID 1370171.
  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. 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.
  10. 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.
  11. 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.
  12. Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A (June 2014). "Concise review: evidence for CD34 as a common marker for diverse progenitors". Stem Cells. 32 (6): 1380–1389. doi:10.1002/stem.1661. PMC 4260088. PMID 24497003.
  13. Nielsen JS, McNagny KM (November 2008). "Novel functions of the CD34 family". Journal of Cell Science. 121 (Pt 22): 3683–3692. doi:10.1242/jcs.037507. PMID 18987355.
  14. 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. PMID 16720896. S2CID 41420678.
  15. Berg EL, Mullowney AT, Andrew DP, Goldberg JE, Butcher EC (February 1998). "Complexity and differential expression of carbohydrate epitopes associated with L-selectin recognition of high endothelial venules". The American Journal of Pathology. 152 (2): 469–477. PMC 1857953. PMID 9466573.
  16. 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. PMID 17459027. S2CID 7630223.
  17. Drew E, Merzaban JS, Seo W, Ziltener HJ, McNagny KM (January 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. PMID 15664158.
  18. Strilić B, Kucera T, Eglinger J, Hughes MR, McNagny KM, Tsukita S, et al. (October 2009). "The molecular basis of vascular lumen formation in the developing mouse aorta". Developmental Cell. 17 (4): 505–515. doi:10.1016/j.devcel.2009.08.011. PMID 19853564.
  19. Blanchet MR, Maltby S, Haddon DJ, Merkens H, Zbytnuik L, McNagny KM (September 2007). "CD34 facilitates the development of allergic asthma". Blood. 110 (6): 2005–2012. doi:10.1182/blood-2006-12-062448. PMID 17557898.
  20. Blanchet MR, Bennett JL, Gold MJ, Levantini E, Tenen DG, Girard M, et al. (September 2011). "CD34 is required for dendritic cell trafficking and pathology in murine hypersensitivity pneumonitis". American Journal of Respiratory and Critical Care Medicine. 184 (6): 687–698. doi:10.1164/rccm.201011-1764OC. PMC 3208601. PMID 21642249.
  21. Ramsfjell 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. PMID 10590054.
  22. 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.
  23. Ebihara Y, Wada M, Ueda T, Xu MJ, Manabe A, Tanaka R, et al. (November 2002). "Reconstitution of human haematopoiesis in non-obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34+CD38- cells expressing Flk2/Flt3". British Journal of Haematology. 119 (2): 525–534. doi:10.1046/j.1365-2141.2002.03820.x. PMID 12406096. S2CID 10040999.
  24. 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.
  25. 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. PMID 8513861.
  26. Chen CZ, Li L, Li M, Lodish HF (October 2003). "The endoglin(positive) sca-1(positive) rhodamine(low) phenotype defines a near-homogeneous population of long-term repopulating hematopoietic stem cells". Immunity. 19 (4): 525–533. doi:10.1016/s1074-7613(03)00265-6. PMID 14563317.
  27. Ogawa M, Tajima F, Ito T, Sato T, Laver JH, Deguchi T (June 2001). "CD34 expression by murine hematopoietic stem cells. Developmental changes and kinetic alterations". Annals of the New York Academy of Sciences. 938 (1): 139–145. Bibcode:2001NYASA.938..139O. doi:10.1111/j.1749-6632.2001.tb03583.x. PMID 11458501. S2CID 83284239.
  28. Tajima F, Sato T, Laver JH, Ogawa M (September 2000). "CD34 expression by murine hematopoietic stem cells mobilized by granulocyte colony-stimulating factor". Blood. 96 (5): 1989–1993. doi:10.1182/blood.V96.5.1989. PMID 10961905.
  29. Hua P, Roy N, de la Fuente J, Wang G, Thongjuea S, Clark K, et al. (December 2019). "Single-cell analysis of bone marrow-derived CD34+ cells from children with sickle cell disease and thalassemia". Blood. 134 (23): 2111–2115. doi:10.1182/blood.2019002301. PMC 7259822. PMID 31697810.
  30. Tamari R, Oran B, Hilden P, Maloy M, Kongtim P, Papadopoulos EB, et al. (May 2018). "Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndrome: Comparison of Outcomes between CD34+ Selected and Unmodified Hematopoietic Stem Cell Transplantation". Biology of Blood and Marrow Transplantation. 24 (5): 1079–1087. doi:10.1016/j.bbmt.2018.01.001. PMC 6529210. PMID 29325829.
  31. Srivastava A, Bapat M, Ranade S, Srinivasan V, Murugan P, Manjunath S, Thamaraikannan P, Abraham S (2010). "Autologous Multiple Injections of in Vitro Expanded Autologous Bone Marrow Stem Cells For Cervical Level Spinal Cord Injury - A Case Report". Journal of Stem Cells and Regenerative Medicine.
  32. 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. PMID 16778155. S2CID 5649484.
  33. 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.
  34. 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
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