![Hematopoiesis simple](https://upload.wikimedia.org/wikipedia/commons/f/f0/Hematopoiesis_simple.svg)
Haematopoiesis (,
from
Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
, 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
cellular components. All cellular blood components are derived from
haematopoietic 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 ...
s.
In a healthy adult person, approximately – new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.
[Semester 4 medical lectures at Uppsala University 2008 by Leif Jansson]
Process
Haematopoietic stem cells (HSCs)
Haematopoietic 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 ...
s (HSCs) reside in the medulla of the bone (
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 ...
) and have the unique ability to give rise to all of the different mature blood cell types and tissues.
HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs so the pool of stem cells is not depleted. This phenomenon is called
asymmetric division. The other daughters of HSCs (
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, ...
and
lymphoid
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
progenitor cells) can follow any of the other differentiation pathways that lead to the production of one or more specific types of blood cell, but cannot renew themselves. The pool of progenitors is
heterogeneous
Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, siz ...
and can be divided into two groups; long-term self-renewing HSC and only transiently self-renewing HSC, also called short-terms. This is one of the main vital processes in the body.
Cell types
All blood cells are divided into three lineages.
*
Red blood cell
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 ...
s, also called erythrocytes, are the oxygen-carrying
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s.
Erythrocytes
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 ...
are functional and are released into the blood. The number of reticulocytes, immature red blood cells, gives an estimate of the rate of
erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is stimulated by decrea ...
.
*
Lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s are the cornerstone of the adaptive immune system. They are derived from common lymphoid progenitors. The lymphoid lineage is composed of
T-cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...
s,
B-cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
s and
natural killer cells
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...
. This is
lymphopoiesis
Lymphopoiesis (lĭm'fō-poi-ē'sĭs) (or lymphocytopoiesis) is the generation of lymphocytes, which are one of the five types of white blood cells (WBCs). It is more formally known as lymphoid hematopoiesis.
Disruption in lymphopoiesis can lead t ...
.
* Cells of the myeloid lineage, which include
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 ...
s,
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 ...
s and
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s, are derived from common myeloid progenitors, and are involved in such diverse roles as
innate immunity
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
and
blood clotting
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
. This is
myelopoiesis
In hematology, myelopoiesis in the broadest sense of the term is the production of bone marrow and of all cells that arise from it, namely, all blood cells. In a narrower sense, myelopoiesis also refers specifically to the regulated formation of my ...
.
Granulopoiesis
Granulopoiesis (or granulocytopoiesis) is a part of haematopoiesis, that leads to the production of granulocytes. A granulocyte, also referred to as a polymorphonuclear leukocyte (PMN), is a type of white blood cell that has multi lobed nuclei, u ...
(or granulocytopoiesis) is haematopoiesis of granulocytes, except of
mast cell
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...
s which are granulocytes but with an extramedullar maturation.
Thrombopoiesis
Thrombopoiesis is the formation of thrombocytes (blood platelets) in the bone marrow. Thrombopoietin is the main regulator of thrombopoiesis. Thrombopoietin affects most aspects of the production of platelets. This includes self-renewal and expan ...
is haematopoiesis of
thrombocytes (platelets).
Terminology
Between 1948 and 1950, the Committee for Clarification of the Nomenclature of Cells and Diseases of the Blood and Blood-forming Organs issued reports on the nomenclature of blood cells. An overview of the terminology is shown below, from earliest to final stage of development:
*
oot
''The Legend of Zelda: Ocarina of Time'' is an action-adventure game developed and published by Nintendo for the Nintendo 64. It was released in Japan and North America in November 1998, and in PAL regions the following month. ''Ocarina of Tim ...
last
* pro
oot
''The Legend of Zelda: Ocarina of Time'' is an action-adventure game developed and published by Nintendo for the Nintendo 64. It was released in Japan and North America in November 1998, and in PAL regions the following month. ''Ocarina of Tim ...
yte
*
oot
''The Legend of Zelda: Ocarina of Time'' is an action-adventure game developed and published by Nintendo for the Nintendo 64. It was released in Japan and North America in November 1998, and in PAL regions the following month. ''Ocarina of Tim ...
yte
* meta
oot
''The Legend of Zelda: Ocarina of Time'' is an action-adventure game developed and published by Nintendo for the Nintendo 64. It was released in Japan and North America in November 1998, and in PAL regions the following month. ''Ocarina of Tim ...
yte
* mature cell name
The root for erythrocyte colony-forming units (CFU-E) is "rubri", for granulocyte-monocyte colony-forming units (CFU-GM) is "granulo" or "myelo" and "mono", for lymphocyte colony-forming units (CFU-L) is "lympho" and for megakaryocyte colony-forming units (CFU-Meg) is "megakaryo". According to this terminology, the stages of red blood cell formation would be: rubriblast, prorubricyte, rubricyte, metarubricyte, and erythrocyte. However, the following nomenclature seems to be, at present, the most prevalent:
Osteoclast
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...
s also arise from hemopoietic cells of the monocyte/neutrophil lineage, specifically CFU-GM.
Location
In developing embryos, blood formation occurs in aggregates of blood cells in the yolk sac, called
blood islands
Blood islands are structures around the developing embryo which lead to many different parts of the circulatory system. Blood islands arise external to the developing embryo on the umbilical vesicle, allantois, connecting stalk and chorion. Th ...
. As development progresses, blood formation occurs in the
spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . ,
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
and
lymph nodes
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
.
When
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 ...
develops, it eventually assumes the task of forming most of the blood cells for the entire organism.
However, maturation, activation, and some proliferation of lymphoid cells occurs in the spleen,
thymus
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
, and lymph nodes. In children, haematopoiesis occurs in the marrow of the long bones such as the femur and tibia. In adults, it occurs mainly in the pelvis, cranium, vertebrae, and sternum.
Extramedullary
In some cases, the liver, thymus, and spleen may resume their haematopoietic function, if necessary. This is called ''
extramedullary haematopoiesis''. It may cause these organs to increase in size substantially. During fetal development, since bones and thus the bone marrow develop later, the liver functions as the main haematopoetic organ. Therefore, the liver is enlarged during development. Extramedullary haematopoiesis and myelopoiesis may supply
leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
in
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
and inflammation during adulthood. Splenic
macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
and
adhesion molecules
Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
may be involved in regulation of extramedullary myeloid cell generation in
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
.
Maturation
![Hematopoiesis (human) diagram en](https://upload.wikimedia.org/wikipedia/commons/1/1f/Hematopoiesis_%28human%29_diagram_en.svg)
As a stem cell matures it undergoes changes in
gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
that limit the cell types that it can become and moves it closer to a specific cell type (
cellular 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 multicellular ...
). These changes can often be tracked by monitoring the presence of proteins on the surface of the cell. Each successive change moves the cell closer to the final cell type and further limits its potential to become a different cell type.
Cell fate determination
Two models for haematopoiesis have been proposed: determinism and stochastic theory. For the stem cells and other undifferentiated blood cells in the bone marrow, the determination is generally explained by the ''determinism'' theory of haematopoiesis, saying that colony stimulating factors and other factors of the haematopoietic microenvironment determine the cells to follow a certain path of cell differentiation.
This is the classical way of describing haematopoiesis. In ''stochastic'' ''theory,'' undifferentiated blood cells differentiate to specific cell types by randomness. This theory has been supported by experiments showing that within a population of mouse haematopoietic progenitor cells, underlying stochastic variability in the distribution of
Sca-1
Sca-1 stands for "Stem cells antigen-1" (official gene symbol: Ly6a). It consist of 18-kDa mouse glycosyl phosphatidylinositol-anchored cell (biology), cell surface protein (GPI-AP) of the LY6 gene family. It is the common biological marker used t ...
, a
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
factor, subdivides the population into groups exhibiting variable rates of
cellular 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 multicellular ...
. For example, under the influence of
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 ...
(an erythrocyte-differentiation factor), a subpopulation of cells (as defined by the levels of Sca-1) differentiated into
erythrocytes
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 ...
at a sevenfold higher rate than the rest of the population. Furthermore, it was shown that if allowed to grow, this subpopulation re-established the original subpopulation of cells, supporting the theory that this is a stochastic, reversible process. Another level at which stochasticity may be important is in the process of apoptosis and self-renewal. In this case, the haematopoietic microenvironment prevails upon some of the cells to survive and some, on the other hand, to perform
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
and die.
By regulating this balance between different cell types, the bone marrow can alter the quantity of different cells to ultimately be produced.
Growth factors
![Hematopoietic growth factors](https://upload.wikimedia.org/wikipedia/commons/a/a1/Hematopoietic_growth_factors.png)
Red and white blood cell production is regulated with great precision in healthy humans, and the production of leukocytes is rapidly increased during infection. The proliferation and self-renewal of these cells depend on growth factors. One of the key players in self-renewal and development of haematopoietic cells is
stem cell factor
Stem cell factor (also known as SCF, KIT-ligand, KL, or steel factor) is a cytokine that binds to the c-KIT receptor (CD117). SCF can exist both as a transmembrane protein and a soluble protein. This cytokine plays an important role in hematopoie ...
(SCF), which binds to the c-kit receptor on the HSC. Absence of SCF is lethal. There are other important
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
growth factors which regulate the proliferation and maturation, 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
IL-2
The Ilyushin Il-2 (Russian: Илью́шин Ил-2) is a ground-attack plane that was produced by the Soviet Union in large numbers during the Second World War. The word ''shturmovík'' ( Cyrillic: штурмовик), the generic Russian term ...
,
IL-3,
IL-6,
IL-7. Other factors, termed
colony-stimulating factors
Colony-stimulating factors (CSFs) are secreted glycoproteins that bind to receptor proteins on the surfaces of hemopoietic stem cells, thereby activating intracellular signaling pathways that can cause the cells to proliferate and differentiate ...
(CSFs), specifically stimulate the production of committed cells. Three CSFs are
granulocyte-macrophage CSF (GM-CSF),
granulocyte CSF (G-CSF) and
macrophage CSF (M-CSF). These stimulate
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 ...
formation and are active on either
progenitor cells
In genealogy, the progenitor (rarer: primogenitor; german: Stammvater or ''Ahnherr'') is the – sometimes legendary – founder of a family, line of descent, clan or tribe, noble house, or ethnic group..
Ebenda''Ahnherr:''"Stammvater eines G ...
or end product cells.
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 ...
is required for a myeloid progenitor cell to become an erythrocyte.
[Molecular cell biology. Lodish, Harvey F. 5. ed. : – New York : W. H. Freeman and Co., 2003, 973 s. b ill.
----] On the other hand,
thrombopoietin
Thrombopoietin (THPO) also known as megakaryocyte growth and development factor (MGDF) is a protein that in humans is encoded by the ''THPO'' gene.
Thrombopoietin is a glycoprotein hormone produced by the liver and kidney which regulates the pro ...
makes myeloid progenitor cells differentiate to
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 ...
s (
thrombocyte
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
-forming cells).
[ The diagram to the right provides examples of cytokines and the differentiated blood cells they give rise to.
]
Transcription factors
Growth factors initiate signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
pathways, which lead to activation of transcription factors
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 func ...
. Growth factors elicit different outcomes depending on the combination of factors and the cell's stage of differentiation. For example, long-term expression of PU.1
Transcription factor PU.1 is a protein that in humans is encoded by the ''SPI1'' gene.
Function
This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. The nuclear pro ...
results in myeloid commitment, and short-term induction of PU.1 activity leads to the formation of immature eosinophils. Recently, it was reported that transcription factors such as NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
can be regulated by microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s (e.g., miR-125b) in haematopoiesis.
The first key player of differentiation from HSC to a multipotent progenitor (MPP) is transcription factor CCAAT-enhancer binding protein α (C/EBP
CCAAT-enhancer-binding proteins (or C/EBPs) is a family of transcription factors composed of six members, named from C/EBPα to C/EBPζ. They promote the expression of certain genes through interaction with their promoters. Once bound to DNA, C ...
α). Mutations in C/EBPα are associated with acute myeloid leukaemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include ...
. From this point, cells can either differentiate along the Erythroid-megakaryocyte lineage or lymphoid and myeloid lineage, which have common progenitor, called lymphoid-primed multipotent progenitor. There are two main transcription factors. PU.1 for Erythroid-megakaryocyte lineage and GATA-1, which leads to a lymphoid-primed multipotent progenitor.
Other transcription factors include Ikaros (B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
development), and Gfi1
Zinc finger protein Gfi-1 is a transcriptional repressor that in humans is encoded by the ''GFI1'' gene. It is important normal hematopoiesis.
Interactions
GFI1 has been shown to interact
Advocates for Informed Choice, doing business as, ...
(promotes Th2 development and inhibits Th1) or IRF8
Interferon regulatory factor 8 (IRF8) also known as interferon consensus sequence-binding protein (ICSBP), is a protein that in humans is encoded by the ''IRF8'' gene. IRF8 is a transcription factor that plays critical roles in the regulation of l ...
(basophils
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
and mast cell
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...
s). Significantly, certain factors elicit different responses at different stages in the haematopoiesis. For example, CEBPα in neutrophil development or PU.1
Transcription factor PU.1 is a protein that in humans is encoded by the ''SPI1'' gene.
Function
This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. The nuclear pro ...
in monocytes and dendritic cell development. It is important to note that processes are not unidirectional: differentiated cells may regain attributes of progenitor cells.
An example is PAX5
Paired box protein Pax-5 is a protein that in humans is encoded by the ''PAX5'' gene.
Function
The PAX5 gene is a member of the paired box (PAX) family of transcription factors. The central feature of this gene family is a novel, highly cons ...
factor, which is important in B cell development and associated with lymphomas. Surprisingly, pax5 conditional knock out mice allowed peripheral mature B cells to de-differentiate to early bone marrow progenitors. These findings show that transcription factors act as caretakers of differentiation level and not only as initiators.
Mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
in transcription factors are tightly connected to blood cancers, as acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...
(AML) or acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
(ALL). For example, Ikaros is known to be regulator of numerous biological events. Mice with no Ikaros lack B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s, Natural killer
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...
and T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s. Ikaros has six zinc finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...
s domains, four are conserved DNA-binding domain
A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a genera ...
and two are for dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ...
ization. Very important finding is, that different zinc fingers are involved in binding to different place in DNA and this is the reason for pleiotropic effect of Ikaros and different involvement in cancer, but mainly are mutations associated with BCR-Abl
The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells). This chromosome is defective and unusually short becaus ...
patients and it is bad prognostic marker.
Other animals
In some vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
s, haematopoiesis can occur wherever there is a loose stroma of connective tissue and slow blood supply, such as the gut, spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . or kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
.
Unlike eutherian mammals, the liver of newborn marsupials is actively haematopoietic.[Old JM, Selwood L, Deane EM (2003). A histological investigation of the lymphoid and immunohaematopoietic tissues of the adult stripe-faced dunnart (''Sminthopsis macroura''). Cells Tissues Organs. 173(2), 115-121. DOI: 10.1159/000068946]
See also
* Clonal hematopoiesis Clonal hematopoiesis of indeterminate potential, or CHIP, is a common aging-related phenomenon in which hematopoietic stem cells (HSCs) or other early blood cell progenitors contribute to the formation of a genetically distinct subpopulation of bl ...
* Erythropoiesis-stimulating agents
Erythropoiesis-stimulating agents (ESA) are medications which stimulate the bone marrow to make red blood cells. They are used to treat anemia due to end stage kidney disease, chemotherapy, major surgery, or certain treatments in HIV/AIDS. In t ...
* Haematopoietic stimulants:
** Granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
Functional ...
** Granulocyte macrophage colony-stimulating factor
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts th ...
* Leukocyte extravasation
Leukocyte extravasation (also commonly known as leukocyte adhesion cascade or diapedesis – the passage of cells through the intact vessel wall) is the movement of leukocytes out of the circulatory system and towards the site of tissue damage or ...
References
Further reading
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External links
Hematopoietic cell lineage
in KEGG
KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of databases dealing with genomes, biological pathways, diseases, drugs, and chemical substances. KEGG is utilized for bioinformatics research and education, including data analysis i ...
Hematopoiesis and bone marrow histology
{{Cytokines
Hematopoiesis
Histology