CD34

Last updated
CD34
Identifiers
Aliases CD34 , entrez:947, CD34 molecule
External IDs OMIM: 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 Mb Chr 1: 194.62 – 194.64 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Contents

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

Related Research Articles

Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Aplastic anemia is associated with cancer and various cancer syndromes. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.

<span class="mw-page-title-main">Hematopoietic stem cell transplantation</span> Medical procedure to replace blood or immune stem cells

Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce additional normal blood cells. It may be autologous, allogeneic or syngeneic.

<span class="mw-page-title-main">Graft-versus-host disease</span> Medical condition

Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.

<span class="mw-page-title-main">Hematopoietic stem cell</span> Stem cells that give rise to other blood cells

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm.

<span class="mw-page-title-main">Interleukin 3</span> Protein-coding gene in the species Homo sapiens

Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein contains 152 amino acids and its molecular weight is 17 kDa. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. The major function of IL-3 cytokine is to regulate the concentrations of various blood-cell types. It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors. It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.

Cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders such as cancer. There is growing interest from cell therapeutics companies in developing genetically modified allogenic natural killer cells from umbilical cord blood as an alternative to CAR T cell therapies for rare diseases.

<span class="mw-page-title-main">Adult stem cell</span> Multipotent stem cell in the adult body

Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells, they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.

<span class="mw-page-title-main">Extramedullary hematopoiesis</span> Medical condition

Extramedullary hematopoiesis refers to hematopoiesis occurring outside of the medulla of the bone. It can be physiologic or pathologic.

Hemangioblasts are the multipotent precursor cells that can differentiate into both hematopoietic and endothelial cells. In the mouse embryo, the emergence of blood islands in the yolk sac at embryonic day 7 marks the onset of hematopoiesis. From these blood islands, the hematopoietic cells and vasculature are formed shortly after. Hemangioblasts are the progenitors that form the blood islands. To date, the hemangioblast has been identified in human, mouse and zebrafish embryos.

<span class="mw-page-title-main">CD164</span> Protein-coding gene in the species Homo sapiens

Sialomucin core protein 24 also known as endolyn or CD164 is a protein that in humans is encoded by the CD164 gene. CD164 functions as a cell adhesion molecule.

<span class="mw-page-title-main">CD135</span> Protein-coding gene in the species Homo sapiens

Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3, receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).

<span class="mw-page-title-main">FMS-like tyrosine kinase 3 ligand</span> Protein-coding gene in the species Homo sapiens

Fms-related tyrosine kinase 3 ligand (FLT3LG) is a protein which in humans is encoded by the FLT3LG gene.

<span class="mw-page-title-main">CFU-GEMM</span>

CFU-GEMM is a colony forming unit that generates myeloid cells. CFU-GEMM cells are the oligopotential progenitor cells for myeloid cells; they are thus also called common myeloid progenitor cells or myeloid stem cells. "GEMM" stands for granulocyte, erythrocyte, monocyte, megakaryocyte.

Stem cell markers are genes and their protein products used by scientists to isolate and identify stem cells. Stem cells can also be identified by functional assays. Below is a list of genes/protein products that can be used to identify various types of stem cells, or functional assays that do the same. The initial version of the list below was obtained by mining the PubMed database as described in

KSL cells in cell biology are an early form of mouse/murine hematopoietic stem cells. Characteristics are Kit (+), Sca-1 (+) and Lin (-). HSCs [Hematopoietic stem cells] in murine cultures show phenotypic markers as being CD34-, CD150+, and Flt3- for LTR [long-term reconstitution]. These phenotypic markers are used when purifying hematopoietic stem cells from the many other differentiated cells in the bone marrow.

<span class="mw-page-title-main">Mesenchymal stem cell</span> Multipotent, non-hematopoietic adult stem cells present in multiple tissues

Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts, chondrocytes, myocytes and adipocytes.

<span class="mw-page-title-main">Haematopoietic system</span>

The haematopoietic system is the system in the body involved in the creation of the cells of blood.

Many human blood cells, such as red blood cells (RBCs), immune cells, and even platelets all originate from the same progenitor cell, the hematopoietic stem cell (HSC). As these cells are short-lived, there needs to be a steady turnover of new blood cells and the maintenance of an HSC pool. This is broadly termed hematopoiesis. This event requires a special environment, termed the hematopoietic stem cell niche, which provides the protection and signals necessary to carry out the differentiation of cells from HSC progenitors. This niche relocates from the yolk sac to eventually rest in the bone marrow of mammals. Many pathological states can arise from disturbances in this niche environment, highlighting its importance in maintaining hematopoiesis.

In the immune system, veto cells are white blood cells that have a selective immunomodulation properties. Veto cells were first described in 1979 as cells that “can prevent generation of cytotoxic lymphocytes by normal spleen cells against self-antigens”. Hence, veto cells delete T cells that recognize the veto cells.

Since haematopoietic stem cells cannot be isolated as a pure population, it is not possible to identify them under a microscope. Therefore, there are many techniques to isolate haematopoietic stem cells (HSCs). HSCs can be identified or isolated by the use of flow cytometry where the combination of several different cell surface markers is used to separate the rare HSCs from the surrounding blood cells. HSCs lack expression of mature blood cell markers and are thus, called Lin-. Lack of expression of lineage markers is used in combination with detection of several positive cell-surface markers to isolate HSCs. In addition, HSCs are characterized by their small size and low staining with vital dyes such as rhodamine 123 or Hoechst 33342.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000174059 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 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. 1 2 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. 1 2 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.

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