Hematopoiesis is also in American English; Sometimes H (the hemopoiesis ) is the formation of blood from the cellular components. All cellular blood components are derived from hematopoietic stem cells. [2] In a healthy adult individual, approximately 10 11 -10 12 new blood cells are produced daily to maintain steady-state levels in the peripheral circulation.
process
hematopoietic stem cells (HSCs)
Hematopoietic stem cells (HSCs) reside in the marrow of the bone ( bone marrow ) and have the unique ability to give rise to all the different mature blood cell types and tissues. [2] 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 partitioning. [5] Other daughters of HSCs ( myeloid and lymphoid progenitor cells) can follow any other differentiation path that leads to the production of one or more specific types of blood cells, but cannot renew themselves. Breeders’ pool is heterogeneous and it can be divided into two groups; Long-term self-renewal HSC and only transiently self-renew HSC, also called short-term. [6] It is one of the main vital processes in the body.
cell type
All blood cells are divided into three lineages.
- Red blood cells, also known as erythrocytes, are oxygen-carrying cells. Erythrocytes are functional and are released into the blood. The number of reticulocytes, and immature red blood cells, gives an estimate of the rate of erythropoiesis.
- Lymphocytes are the cornerstone of the adaptive immune system. They are derived from common lymphoid progenitors. The lymphoid lineage is composed of T-cells, B-cells, and natural killer cells. This is lymphopoiesis.
- Cells of the myeloid lineage, which include granulocytes, megakaryocytes, and macrophages, are derived from common myeloid progenitors and are involved in diverse roles such as innate immunity and blood clotting. This is myelopoiesis.
Granulopoiesis (or granulocytopoiesis) is the hematopoiesis of granulocytes, except for mast cells which are granulocytes but with an extramedullary maturation. [8]
Megakaryocytopoiesis is the hematopoiesis of megakaryocytes.
Glossary
Between 1948 and 1950, the Committee for the Clarification of the Nomenclature of Cells and Diseases of the Blood and Blood-Forming Organs issued the Report on the Nomenclature of Blood Cells. [9] [10] An overview of the terminology is shown below, from the early to late stages of development:
- [root] explode
- pro [root] site
- [root] site
- meta [root] site
- mature cell name
The root is “rhubarb” for erythrocyte colony-forming units (CFU-E), “granule” or “myelo” for lymphocyte colony-forming units (CFU-GM), and “mono” for granulocyte-monocyte colony-forming units (CFU-GM). . (CFU-l) is “lymph” and “megakaryocyte” for megakaryocyte colony-forming units (CFU-meg). According to this terminology, the stages of red blood cell formation would be rubriblast, prorubrocyte, rubrocyte, metarubrocyte, and erythrocyte. However, the following nomenclature appears to be the most prevalent at present:
| Committee | “lymph” | “Rubric” | “granule” or “Melo” | “mono” | “megakaryo” |
|---|---|---|---|---|---|
| genealogy | lymphoid | myeloid | myeloid | myeloid | myeloid |
| CFU | CFU-l | CFU-GEMM → CFU-E | cfu-gemm → cfu-gm → cfu-g | cfu-gemm → cfu-gm → cfu-m | CFU-GEMM → CFU-MAG |
| process | lymphocytopoiesis | erythropoiesis | granulocytopoiesis | monocytopoiesis | thrombocytopoiesis |
| [root] explode | lymphoblast | proerythroblast | myeloblast | monoblast | megakaryoblast |
| pro [root] site | prolymphocyte | polychromatophilic erythrocyte | promyelocyte | promonocyte | promegakaryocyte |
| [root] site | – | normoblast | Casino / neutro / basophilic myelocyte | megakaryocyte | |
| meta [root] site | large lymphocyte | reticulocyte | eosinophilic/neutrophilic/basophilic metamyelocyte, eosinophilic/neutrophilic/basophilic band cell | early monocyte | – |
| mature cell name | small lymphocyte | erythrocyte | Granulocytes (Eosino / Neutro / Basophil) | Mononuclear cell | thrombocytes (platelets) |
Osteoclasts also arise from hemopoietic cells of the monocyte/neutrophil lineage, specifically CFU-GM.
place
Sites of hematopoiesis (human) in the prenatal and postnatal periods
In developing embryos, blood is formed in clusters of blood cells in the yolk sac, called blood islands. As development progresses, blood builds up in the spleen, liver, and lymph nodes. When bone marrow develops, it eventually takes over the task of making most of the blood cells for the whole organism. [2] However, maturation, activation, and some proliferation of lymphoid cells occur in the spleen, thymus, and lymph nodes. In children, hematopoiesis occurs in the marrow of long bones such as the femur and tibia. In adults, it mainly occurs in the pelvis, cranium, vertebrae, and sternum. [1 1]
extramedullary
In some cases, if necessary, the liver, thymus, and spleen can resume their hematopoietic function. This is called extramedullary hematopoiesis. This can lead to a substantial increase in the size of these organs. During embryonic development, as bones and thus bone marrow develop later, the liver serves as the main hematopoietic organ. Therefore, the liver enlarges during development. [12] Extramedullary hematopoiesis and myelopoiesis may supply leukocytes in cardiovascular disease and inflammation during adulthood. [13] [14] Splenic macrophages and adhesion molecules may be involved in the regulation of extramedullary myeloid cell generation in heart disease. [15] [16]
maturity
A more detailed and comprehensive diagram showing the development of the different blood cells in humans.
- Morphological features of hematopoietic cells are visualized with Wright’s stain, May–Giemsa stain or May–Grünwald–Giemsa stain. Alternate names of some cells are shown in parentheses.
- Some cells may have more than one distinct form. In these cases, more than one representation of the same cell is included.
- Together, monocytes and lymphocytes comprise agranulocytes, as opposed to granulocytes (basophils, neurophils, and eosinophils) that are produced during granulopoiesis.
- B, N and E. stand for basophilic, neutrophilic and eosinophilic, respectively – as in basophilic promyelocyte. For lymphocytes, T and B are the actual designations.
- The polychromatic erythrocyte (reticulocyte) at right shows its characteristic appearance when stained with methylene blue or azure B.
- The erythrocyte on the right is a more accurate representation of its appearance in reality when viewed through a microscope.
- Other cells that are derived from monocyte: osteoclast, microglia (central nervous system), Langerhans cell (epidermis), Kupffer cell (liver).
- For clarity, T and B lymphocytes are divided to indicate that the plasma cell originates from a B-cell. Note that there is no difference in the appearance of B- and T-cells unless specific staining is applied.
As a stem cell matures, it undergoes changes in gene expression that limit the cell types it can become and drive it closer to a specific cell type (cellular differentiation). These changes can often be tracked by monitoring the presence of proteins on the cell surface. Each successive change moves the cell closer to the final cell type and further limits its ability to become a distinct cell type.
cell fate determination
Two models have been proposed for hematopoiesis: determinism and the stochastic theory. [17] For stem cells and other undifferentiated blood cells in the bone marrow, a determination is generally explained by the determinism theory of hematopoiesis, which states that colony-stimulating factors and other factors in the hematopoietic microenvironment cause cells to follow a fixed path. set to do. cell differentiation. [2] This is the classical way of describing hematopoiesis. In stochastic theory, Differentiate to specific cell types by a similar irregularity of blood cells. This theory is supported by experiments showing that, within a population of mouse hematopoietic progenitor cells, inherent stochastic variability in the distribution of Sca-1, a stem cell factor, divides the population into groups exhibiting variable rates of cellular differentiation.
subdivides into For example, under the influence of erythropoietin (an erythrocyte-differentiation factor), a subpopulation of cells (as defined by levels of SCA-1) differentiated into erythrocytes at a rate seven times higher than the rest of the population. . [18]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 processes of apoptosis and self-renewal. In this case, the hematopoietic microenvironment predominates on some cells to survive and on the others, to undergo apoptosis and die. [2] By regulating this balance between different cell types, the bone marrow can change the number of different cells it ultimately produces.
growth factors
Diagram including some of the important cytokines that determine what type of blood cell will be made. [20] SCF = stem cell factor; TPO = thrombopoietin; IL = interleukin; GM-CSF = granulocyte macrophage-colony stimulating factor; Epo = erythropoietin; M-CSF = macrophage-colony stimulating factor; G-CSF = granulocyte-colony stimulating factor; SDF-1 = stromal cell-derived factor-1; FLT-3 ligand = FMS-like tyrosine kinase 3 ligand; TNF-a = tumor necrosis factor-alpha; TGFβ = transforming growth factor beta
Red and white blood cell production in healthy humans is regulated with great precision, and the production of leukocytes increases rapidly during infection. The proliferation and self-renewal of these cells depend on growth factors. One of the key players in the self-renewal and development of hematopoietic cells is stem cell factor (SCF), [22]which binds to the c-kit receptor on HSCs. The absence of SCF is fatal. Other important glycoproteins are growth factors that control proliferation and maturation, such as the interleukins IL-2, IL-3, IL-6, and IL-7. Other factors, called colony-stimulating factors (CSFs), specifically stimulate the production of committed cells. The three CSFs are granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), and macrophage CSF (M-CSF). [23] These stimulate granulocyte formation and act on either progenitor cells or end-product cells.
Erythropoietin is required for a myeloid progenitor cell to become an erythrocyte. [20] On the other hand, thrombopoietin differentiates myeloid progenitor cells from megakaryocytes (thrombocyte-forming cells). [20] The diagram on the right provides examples of cytokines and the differentiated blood cells they produce. [24]
transcription factors
Growth factors initiate signal transduction pathways, which lead to the activation of transcription factors. Growth factors achieve different results depending on the combination of factors and the stage of differentiation of the cell. For example, long-term expression of PU.1 leads to myeloid commitment, and short-term induction of PU.1 activity leads to the formation of immature eosinophils. [25] Recently, it was reported that transcription factors such as NF-κB can be regulated by microRNAs (eg, miR-125b) in hematopoiesis. [26]
The first major player in the differentiation of HSC to multipotent progenitor (MPP) is the transcription factor CCAAT-enhancer binding protein α (C/EBPα). Mutations in C/EBPα are associated with acute myeloid leukemia. [27] From this point, cells can differentiate either along the erythroid-megakaryocyte lineage or along the lymphoid and myeloid lineages, which have common progenitors, called lymphoid-primed multipotent progenitors. There are two main transcription factors. PU.1 for the erythroid-megakaryocyte lineage and GATA-1, which leads to a lymphoid-primed multipotent progenitor.
Other transcription factors include Ikaros [28] (B cell development), Gfi1 [29] (promotes Th2 development and inhibits Th1), or IRF8 [30] (basophils and mast cells). Importantly, some factors elicit different responses at different stages in hematopoiesis. For example, CEBPα in neutrophil development or PU.1 in monocytes and dendritic cell development. It is important to note that the processes are not unidirectional: differentiated cells can recapture characteristics of progenitor cells.
One example is the PAX5 factor, which is important in B cell development and has been associated with lymphoma. [31] Intriguingly, pax5 conditional knockout mice allowed peripheral mature B cells to differentiate from early bone marrow progenitors. These findings suggest that transcription factors act as activators of the differentiation stage and not simply as initiators. [32]
Mutations in transcription factors are tightly linked to blood cancers, such as acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). For example, Ikaros is known to be the regulator of many biological phenomena. Mice without Ikaros lack B cells, natural killer and T cells. [33] Ikaros has six zinc finger domains, four conserved DNA-binding domains, and two for dimerization. [34] The very important finding that different zinc fingers are involved in binding to different sites in DNA is the reason for the pleiotropic effect of Ikaros and the different involvement in cancer, but mainly from BCR-ABL patients. There are associated mutations and it is a poor prognostic marker. [35]
other animals
In some vertebrates, hematopoiesis can occur wherever there is a loose stroma of connective tissue and a slow blood supply, such as the intestine, spleen, or kidney.
