Hematopoietic stem cells (HSCs) are specialized cells responsible for generating all types of blood and immune cells throughout an individual’s life. These cells reside primarily in the bone marrow, continuously replenishing the body’s blood supply. To identify and distinguish HSCs from other cells, scientists rely on “markers,” which are unique identifying molecules found on the cell surface. These markers act like cellular barcodes, allowing researchers to pinpoint and study these rare cells. Understanding and applying these markers is important for scientific research and medical treatments involving HSCs.
Identifying Hematopoietic Stem Cells
Identifying hematopoietic stem cells presents a challenge due to their scarcity within tissues like bone marrow and blood. To overcome this, researchers utilize specific markers, which are proteins located on the cell’s outer membrane. These surface proteins serve as distinct “signatures” that differentiate HSCs from more mature blood cells or other stem cell populations.
The accurate identification of HSCs requires a combination of both positive and negative markers. Positive markers indicate the presence of a specific protein on the cell surface, while negative markers indicate the absence of proteins found on differentiated, mature blood cells. By looking for this combination of present and absent markers, scientists can precisely isolate and characterize HSCs, enabling focused study of their properties and functions. This selective process is important for gaining insights into how these cells maintain blood production and respond to various physiological demands.
Key HSC Markers and Their Significance
A positive marker for hematopoietic stem and progenitor cells is CD34. CD34 is expressed on HSCs and progenitors from early fetal development through adulthood, serving as a primary identifier for these cell populations in bone marrow, umbilical cord blood, and peripheral blood. While CD34 is a strong indicator, it is also found on endothelial cells, requiring additional markers for precise HSC identification.
CD38 is used in conjunction with CD34 to refine HSC identification. HSCs that are CD34-positive but CD38-negative (CD34+CD38-) are considered more primitive and possess a higher capacity for self-renewal and differentiation. This combination helps distinguish primitive HSCs from more committed progenitor cells that express CD38. Recent research indicates that CD34+CD38- cells play an important role in regenerating blood and immune systems following treatments like chemotherapy or radiation therapy.
Another marker associated with primitive HSCs in humans is CD90. The co-expression of CD90 on CD34+CD38- cells defines a primitive HSC population, while CD34+CD38-CD90- cells are multipotent progenitors. CD90 is also expressed on endothelial cells and smooth muscle cells, similar to CD34, requiring its use in combination with other markers for specific HSC isolation.
CD133 is an alternative or additional marker used for identifying stem and progenitor cells. In addition to these positive markers, the concept of “lineage negative” (Lin-) is used to define primitive stem cells. This signifies the absence of markers expressed on differentiated blood cells, such as CD2, CD3, CD11b, CD14, CD16, CD19, CD24, CD56, CD66b, and CD235, which helps to exclude mature blood cells from the stem cell population.
How HSC Markers Are Used
HSC markers are used in scientific research to isolate pure populations of hematopoietic stem cells. Researchers utilize these markers to study the biology of HSCs, including their capacity for self-renewal and their differentiation into various blood cell types, both in laboratory settings and in living organisms. Techniques like flow cytometry and magnetic-activated cell sorting (MACS) are used to separate cells based on their marker expression, enabling scientists to obtain purified HSC samples for analysis.
In clinical applications, HSC markers are important, particularly in hematopoietic stem cell transplantation. These markers are important for identifying, quantifying, and performing quality control on stem cell grafts used in procedures such as bone marrow transplants. For instance, ensuring a sufficient number of CD34+ cells in a graft is a criterion for selecting umbilical cord blood donors and is a predictor of successful long-term engraftment and hematopoietic reconstitution in patients.
HSC markers also contribute to disease diagnosis and monitoring, such as in blood cancers. They assist in identifying aberrant cell populations characteristic of these diseases and in tracking a patient’s recovery following treatment. Markers also play a role in gene therapy approaches, where they help in targeting or tracking HSCs to deliver therapeutic genes, offering potential for treating inherited immune deficiencies and other conditions.