CFU-GEMM is a

colony forming unit In microbiology, colony-forming unit (CFU, cfu or Cfu) is a unit which estimates the number of microbial cells (bacteria, fungi, viruses etc.) in a sample that are viable, able to multiply via binary fission under the controlled conditions. Count ...

that generates

myeloid Myeloid tissue, in the bone marrow sense of the word '' myeloid'' ('' myelo-'' + ''-oid''), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (''myelo-'' + '' -genous'') is any tissue of, ...

cells. CFU-GEMM cells are the oligopotential

progenitor cell A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor ...

s for myeloid cells; they are thus also called common myeloid progenitor cells or myeloid stem cells. "GEMM" stands for

granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...

erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

megakaryocyte A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In hum ...

. The common myeloid progenitor (CMP) and the common lymphoid progenitor (CLP) are the first branch of

cell differentiation Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellula ...

hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...

after the hemocytoblast (

hematopoietic stem cell 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 t ...

Structure

In current terminology, CFU-S refers to the pluripotent stem cells that can differentiate into all types of blood cells. CFU-S divides into two lineages: the lymphoid precursor (CFU-LSC) and the myeloid precursor (CFU-GEMM). The CFU-GEMM cell is capable of differentiating into white blood cells, red blood cells, and platelets, all of which are normally found in circulating blood. It has been suggested that

eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

s do not derive from the common myeloid progenitor in humans. Hematopoiesis_simple

In the adjacent image, CFU-GEMM is the scientific name for the "common myeloid progenitor" that is responsible for forming all the cells of the myeloid lineages. As observed in the image, CFU-GEMM is capable of producing a diverse set of cells. It matures into the megakaryocyte, erythrocyte, mast cell or myeloblast based on the presence of specific factors that encourage the cell to choose a lineage to follow.

Surface markers

The cells are characterized by expressing the cell surface markers CD33, CD34 and

HLA-DR HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR (Human Leukocyte Antigen – DR isotype) and peptide, generally between 9 and 30 amino acids in ...

. These surface markers are proteins on the surface that are unique to specific cells and certain maturation periods, allowing researchers to differentiate between two different cells as well as what stage the cell is found in its developmental progression.

Development

Growth factors

The differentiation and proliferation of CFU-GEMM are promoted by growth factors, such as

interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...

s and cytokines. IL-3 and GM-CSF as single factors are equally active in stimulating CFU-GEMM, but the combination of both factors produces additive stimulatory effects upon CFU-GEMM. The growth of CFU-GEMM is stimulated by the stem cell factor, or SCF. SCF has been found also to synergize with GM-CSF, IL-6, IL-3, IL-11 or

erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bo ...

to increase the numbers of CFU-GEMM. CFU-GEMM gives rise to

CFU-GM CFU-GM, also known as granulocyte–macrophage progenitor (GMP), is a colony forming unit. It is derived from CFU-GEMM. The "GM" stands for "granulocyte, monocyte". It is the precursor for monoblasts and myeloblasts. Production is stimulated by ...

(leading to

monoblast Monoblasts are the committed progenitor cells that differentiated from a committed macrophage or dendritic cell precursor (MDP) in the process of hematopoiesis. They are the first developmental stage in the monocyte series leading to a macrophage. ...

s and

myeloblast The myeloblast is a unipotent stem cell which differentiates into the effectors of the granulocyte series. It is found in the bone marrow. Stimulation of myeloblasts by G-CSF and other cytokines triggers maturation, differentiation, proliferation a ...

s), CFU-Meg (leading to

megakaryoblast A megakaryoblast is a precursor cell to a promegakaryocyte, which in turn becomes a megakaryocyte during haematopoiesis. It is the beginning of the thrombocytic series. Development The megakaryoblast derives from a CFU-Meg colony unit of pluripot ...

s), and

CFU-E CFU-E stands for Colony Forming Unit-Erythroid. It arises from CFU-GEMM (via BFU-E, which stands for "erythroid burst-forming units") and gives rise to proerythroblasts. Murine CFU-E assay CFU-E is a stage of erythroid development between the ...

(leading to

proerythroblast A proerythroblast (or rubriblast, or pronormoblast) is the earliest of four stages in development of the normoblast. In histology, it is very difficult to distinguish it from the other "-blast" cells (lymphoblast, myeloblast, monoblast, and mega ...

s). The stem cell will follow a specific lineage depending on the presence of certain growth factors and

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

s. The GM-CSF and IL-3 both work together to stimulate production of all lines. When erythropoietin (EPO) is present, red blood cell production from the CFU-GEMM will be activated. G-CSF, M-CSF, IL-5, IL-4, and IL-3 stimulate the production of neutrophils, monocytes, eosinophils, basophils, and platelets, respectively.

Research studies

Since the CFU-GEMM cell is a very early ancestor of the mature cells of the blood, it is not normally found in the blood. While present in

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

, the place where CFU-GEMM is most common is in the

umbilical cord In placental mammals, the umbilical cord (also called the navel string, birth cord or ''funiculus umbilicalis'') is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord is physiologic ...

between a mother and baby. It has been discovered that these cells have a high re plating efficiency, meaning that when taken from the umbilical cord and grown in culture, a high percentage of these cells are able to produce colonies. The results of studies conducted by Carow, Hangoc, and Broxmeyer in 1993 reveal that the CFU-GEMM can be classified as a stem cell due to its high replating efficiency in the presence of certain growth factors and cytokines. The growth and production of CFU-GEMM and BFU-E depend on stimulatory factors from a source of burst-promoting activity (BPA) such as the release of interleukin-1 (IL-1) by

s, a has been studied in 1987. It has also been shown that

fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...

s are capable of secreting these BPAs, however only respond to regulatory molecule such as interleukin-1. The results showed that IL-1 increases the stimulatory effects of CFU-GEMM in a dose-dependent fashion with a maximum efficacy around 140 ng/mL. This study revealed that IL-1 plays an important role in the regulation of the production of stimulatory factors that influence the progenitor cells of

. In another study in 2014, researchers were in search of molecules to stimulate the proliferation of long-term hematopoietic stem cells (LT-HSC). They tested a library of more than 5000 small molecules, with all except one (UM729) suppressing growth. A more potent analog was generated and named UM171. When compared to other similar chemicals, UM171 allowed for more HSC proliferation and lower apoptotic cell number compared to controls, along with a higher number in multipotential progenitors like CFU-GEMM. Furthermore, UM171 did not affect division rate. When used in conjunction with SR1, a known

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

, UM171 allowed for suppression of differentiation and led to increased CFU-GEMM growth. These results suggest that UM171+SR1 together enhance proliferation of progenitor cells and suppress differentiation.

References