CD34 - CD34 molecule |Elisa - Clia - Antibody - Protein

Background

CD34 is a well-known cell surface glycoprotein that is primarily expressed on hematopoietic stem and progenitor cells (HSPCs), as well as on endothelial cells, and is used as a marker to identify early stem cells within the bone marrow and other tissues. This molecule has become an invaluable tool in both research and clinical medicine, particularly in the isolation and characterization of hematopoietic stem cells for bone marrow transplantation, and in the study of angiogenesis due to its presence on vascular endothelium.

The CD34 protein belongs to the family of sialomucin-like adhesion molecules. Initially, it was identified as a marker on hematopoietic progenitor cells and subsequently found to be involved in various physiological processes, such as cell adhesion, cell signaling, and migration. CD34 is a highly glycosylated protein, and its extensive post-translational modifications, including sialylation and O-glycosylation, play important roles in its function, particularly in regulating cell-cell interactions and hematopoietic cell homing.

CD34 expression is highly dynamic, being tightly regulated during hematopoietic development and differentiation. The expression is typically lost as hematopoietic stem cells differentiate into more mature cells, making it an essential marker for identifying early, pluripotent stem cells. Furthermore, CD34 has been implicated in endothelial function, especially in angiogenesis, where it participates in the formation of new blood vessels.

Protein Structure

CD34 is a transmembrane glycoprotein that consists of three distinct domains: an extracellular domain, a transmembrane domain, and a cytoplasmic tail. This structure is consistent with its role as a cell surface receptor involved in adhesion and signaling.

Extracellular Domain:

• The extracellular domain of CD34 is highly glycosylated, with extensive O-linked glycosylation and sialylation. This domain is critical for the adhesion properties of CD34, allowing it to interact with various ligands, particularly those that mediate cell-cell and cell-extracellular matrix interactions.
• The extracellular region is characterized by a sialomucin domain, which gives the protein its mucin-like properties. This domain is highly anionic due to the presence of sialic acids, and it is thought to contribute to the anti-adhesive properties of CD34, particularly by creating a charge repulsion that prevents nonspecific cell aggregation.

Transmembrane Domain:

• The transmembrane domain anchors CD34 to the cell membrane and consists of a typical hydrophobic alpha-helix. This domain is relatively short and plays a role in stabilizing the molecule within the lipid bilayer of the cell membrane.
• The transmembrane domain facilitates interactions with co-receptors and may influence the localization of CD34 within specialized regions of the cell membrane, such as lipid rafts, which are important for signal transduction.

Cytoplasmic Domain:

• The cytoplasmic tail of CD34 is short and lacks any classical signaling motifs. Despite the absence of such motifs, it is believed to participate in signal transduction via interactions with intracellular proteins that mediate the organization of the cytoskeleton and cellular signaling pathways.
• Studies suggest that the cytoplasmic domain of CD34 can bind to ezrin-radixin-moesin (ERM) proteins, linking the cytoskeleton to the plasma membrane, which may be involved in regulating cell shape, movement, and adhesion.

Due to the extensive glycosylation, the molecular weight of CD34 varies between 90 and 120 kDa, depending on the level of post-translational modifications. These modifications, particularly the sialylated glycan chains, are critical for its role in mediating interactions between hematopoietic stem cells and their microenvironment.

Classification and Subtypes

CD34 belongs to the family of sialomucin-like adhesion molecules, which includes other transmembrane proteins with similar mucin-like extracellular domains. Within the CD34 family, several isoforms have been identified, resulting from alternative splicing of the CD34 mRNA.

The primary isoforms of CD34 exhibit slight variations in their extracellular or cytoplasmic domains, and these variations can affect the protein's function and localization. The functional implications of these isoforms, however, are still being studied, but it is likely that they contribute to the diverse roles that CD34 plays in different tissues.

CD34 expression is highly regulated in a cell-type specific manner:

• Hematopoietic stem and progenitor cells (HSPCs) exhibit high levels of CD34 expression during the early stages of hematopoietic development.
• Endothelial cells, particularly those involved in angiogenesis, express CD34, where it serves as a marker of vascular endothelial cells.
• Fibroblastic reticular cells and some other specialized cell types also express CD34 under certain conditions.

Given its expression profile, CD34 is classified into different functional subgroups based on the cell types that express it and the contexts in which it functions. For example, in hematopoiesis, CD34 marks early progenitor cells, while in endothelial biology, it is used to study vascular dynamics and angiogenesis.

Function and Biological Significance

CD34 plays key roles in various biological processes, especially those related to cell adhesion, migration, and signal transduction. Its functions can be divided into several categories:

Hematopoietic Stem Cell Marking:

• CD34 is a widely used marker for hematopoietic stem and progenitor cells (HSPCs). The molecule is highly expressed on the surface of pluripotent stem cells within the bone marrow, allowing researchers and clinicians to isolate these cells for bone marrow transplantation and stem cell therapies.
• As hematopoietic cells differentiate, CD34 expression is progressively lost, making it an essential marker for identifying and enriching early-stage stem cells for transplantation.

Cell Adhesion and Migration:

• CD34 functions as an anti-adhesive molecule due to its heavily glycosylated and sialylated extracellular domain. This property is important for regulating cell interactions within the bone marrow niche and the vascular endothelium, allowing CD34-positive cells to remain mobile and interact with other adhesion molecules such as selectins and integrins.
• The ability of CD34 to modulate cell adhesion and migration is particularly important during hematopoietic cell homing, where stem cells migrate to and engraft in the bone marrow after transplantation.

Endothelial Function and Angiogenesis:

• In endothelial cells, CD34 is involved in angiogenesis, the process of new blood vessel formation. CD34-expressing endothelial cells contribute to the development and maintenance of the vascular system, particularly under conditions of tissue growth or repair, such as in wound healing and tumor angiogenesis.
• CD34 also plays a role in vascular permeability, helping regulate the movement of cells and molecules across the endothelium.

Cell Signaling:

• Although CD34 lacks classical signaling motifs in its cytoplasmic tail, it can interact with intracellular proteins that regulate cytoskeletal organization. These interactions can influence cell shape, motility, and signal transduction pathways that govern cell survival and proliferation.
• The association with ERM proteins links CD34 to the actin cytoskeleton, which is crucial for the dynamic processes of cell migration and adhesion, especially during immune surveillance and stem cell mobilization.

Clinical Issues

CD34 has important clinical implications, particularly in the fields of hematology, stem cell transplantation, and cancer biology.

Hematopoietic Stem Cell Transplantation:

• CD34 is used extensively as a marker to isolate HSPCs from bone marrow, peripheral blood, or umbilical cord blood for transplantation. CD34+ stem cells are enriched and transplanted into patients with hematological malignancies (e.g., leukemia, lymphoma) or bone marrow failure syndromes.
• The ability to specifically isolate CD34+ cells has revolutionized stem cell therapy, allowing for more efficient and targeted transplants with improved patient outcomes.

Angiogenesis in Cancer:

• In the context of tumor angiogenesis, CD34 is used as a marker for newly formed blood vessels within tumors. The expression of CD34 on tumor-associated endothelial cells makes it a valuable tool for studying vascular density and the effectiveness of anti-angiogenic therapies in cancer treatment.
• High levels of CD34 expression in tumors are often associated with poor prognosis, as increased angiogenesis can facilitate tumor growth and metastasis.

Immunological Disorders:

• CD34 expression can be dysregulated in certain autoimmune diseases and inflammatory conditions, where abnormal angiogenesis or immune cell mobilization contributes to disease pathology.
• Investigations into the role of CD34 in inflammatory disorders have pointed to its involvement in modulating endothelial cell interactions with immune cells during chronic inflammation.

Summary

CD34 is a critical molecule with diverse functions in hematopoiesis, endothelial biology, and cell adhesion. Structurally, it is a highly glycosylated transmembrane protein with a sialomucin-like extracellular domain, a transmembrane region, and a short cytoplasmic tail. Its primary role as a marker of hematopoietic stem cells and endothelial cells has made it an indispensable tool in stem cell research, transplantation, and cancer biology. Clinically, CD34 is a key player in stem cell therapies, tumor angiogenesis, and vascular diseases, making it an important target for therapeutic interventions in a wide range of medical conditions.