Haematopoiesis - wikipedia Haematopoiesis Diagram showing the development of different blood cells from haematopoietic stem cell to mature cells More detailed and comprehensive diagram that shows the development of different blood cells in humans. The morphological characteristics of the hematopoietic cells are shown as seen in a Wright 's stain, May - Giemsa stain or May - Grünwald - Giemsa stain. Alternative names of certain cells are indicated between parentheses. Certain cells may have more than one characteristic appearance. In these cases, more than one representation of the same cell has been included. Together, the monocyte and the lymphocytes comprise the agranulocytes, as opposed to the granulocytes ( basophil, neurtophil and eosinophil ) that are produced during granulopoiesis. B., N. and E. stand for Basophilic, Neutrophilic and Eosinophilic, respectively -- as in Basophilic promyelocyte. For lymphocytes, the T and B are actual designations. The polychromatic erythrocyte ( reticulocyte ) at the right shows its characteristic appearance when stained with methylene blue or Azure B. The erythrocyte at the right is a more accurate representation of its appearance in reality when viewed through a microscope. Other cells that arise from the monocyte : osteoclast, microglia ( central nervous system ), Langerhans cell ( epidermis ), Kupffer cell ( liver ). For clarity, the T and B lymphocyte are split to better indicate that the plasma cell arises from the B - cell. Note that there is no difference in the appearance of B - and T - cells unless specific staining is applied. Haematopoiesis ( from Greek αἷμα, `` blood '' and ποιεῖν `` to make '' ; also hematopoiesis in American English ; sometimes also haemopoiesis or hemopoiesis ) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately 10 -- 10 new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation. Contents 1 Haematopoietic stem cells ( HSCs ) 2 Locations 2.1 Extramedullary 2.2 Other vertebrates 3 Maturation 3.1 Cell fate determination 3.2 Growth factors 3.3 Transcription factors 3.4 Myeloid - based model 4 See also 5 References 6 Further reading 7 External links Haematopoietic stem cells ( HSCs ) Haematopoietic stem cells ( HSCs ) reside in the medulla of the bone ( bone marrow ) 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 and lymphoid 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 can not renew themselves. The pool of progenitors is heterogeneous 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. All blood cells are divided into three lineages. Red blood cells, also called erythrocytes, are the oxygen - carrying cells. Erythrocytes are functional and are released into the blood. The number of reticulocytes, 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 such diverse roles as innate immunity and blood clotting. This is myelopoiesis. Granulopoiesis ( or granulocytopoiesis ) is haematopoiesis of granulocytes, except of mast cells which are granulocytes but with an extramedullar maturation. Megakaryocytopoiesis is haematopoiesis of megakaryocytes. Locations Sites of haematopoesis ( human ) in pre - and postnatal periods In developing embryos, blood formation occurs in aggregates of blood cells in the yolk sac, called blood islands. As development progresses, blood formation occurs in the spleen, liver and lymph nodes. When bone marrow 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, 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. Other vertebrates In some vertebrates, haematopoiesis can occur wherever there is a loose stroma of connective tissue and slow blood supply, such as the gut, spleen or kidney. Maturation As a stem cell matures it undergoes changes in gene expression that limit the cell types that it can become and moves it closer to a specific cell type ( cellular differentiation ). 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 hematopoiesis 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, a stem cell factor, subdivides the population into groups exhibiting variable rates of cellular differentiation. For example, under the influence of erythropoietin ( an erythrocyte - differentiation factor ), a subpopulation of cells ( as defined by the levels of Sca - 1 ) differentiated into erythrocytes 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 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 Diagram including some of the important cytokines that determine which type of blood cell will be created. 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 = Tumour necrosis factor - alpha TGFβ = Transforming growth factor beta 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 ( SCF ), which binds to the c - kit receptor on the HSC. Absence of SCF is lethal. There are other important glycoprotein growth factors which regulate the proliferation and maturation, such as interleukins IL - 2, IL - 3, IL - 6, IL - 7. Other factors, termed colony - stimulating factors ( 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 formation and are active on either progenitor cells or end product cells. Erythropoietin is required for a myeloid progenitor cell to become an erythrocyte. On the other hand, thrombopoietin makes myeloid progenitor cells differentiate to megakaryocytes ( thrombocyte - 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 pathways, which lead to activation of transcription factors. 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 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 can be regulated by microRNAs ( 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 α ). Mutations in C / EBPα are associated with acute myeloid leukaemia. 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 development ), and Gfi1 ( promotes Th2 development and inhibits Th1 ) or IRF8 ( basophils and mast cells ). Significantly, certain factors elicit different responses at different stages in the haematopoiesis. For example, CEBPα in neutrophil development or PU. 1 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 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 transcription factors are tightly connected to blood cancers, as acute myeloid leukaemia ( AML ) or acute lymphoblastic leukemia ( ALL ). For example, Ikaros is known to be regulator of numerous biological events. Mice with no Ikaros lack B cells, Natural killer and T cells. Ikaros has six zinc fingers domains, four are conserved DNA - binding domain and two are for dimerization. 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 patients and it is bad prognostic marker. Myeloid - based model For a decade now, the evidence is growing that HSC maturation follows a myeloid - based model instead of the ' classical ' schoolbook dichotomy model. In the latter model, the HSC first generates a common myeloid - erythroid progenitor ( CMEP ) and a common lymphoid progenitor ( CLP ). The CLP produces only T or B cells. The myeloid - based model postulates that HSCs first diverge into the CMEP and a common myelo - lymphoid progenitor ( CMLP ), which generates T and B cell progenitors through a bipotential myeloid - T progenitor and a myeloid - B progenitor stage. The main difference is that in this new model, all erythroid, T and B lineage branches retain the potential to generate myeloid cells ( even after the segregation of T and B cell lineages ). The model proposes the idea of erythroid, T and B cells as specialized types of a prototypic myeloid HSC. 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Jump up ^ Schjerven, H ; McLaughlin, J ; Arenzana, TL ; Frietze, S ; Cheng, D ; Wadsworth, SE ; Lawson, GW ; Bensinger, SJ ; Farnham, PJ ; Witte, ON ; Smale, ST ( Oct 2013 ). `` Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros ''. Nature Immunology. 14 ( 10 ) : 1073 -- 83. doi : 10.1038 / ni. 2707. PMC 3800053. PMID 24013668. Jump up ^ Kawamoto, Wada, Katsura. A revised scheme for developmental pathways of haematopoietic cells : the myeloid - based model. International Immunology 2010. Further reading Godin, Isabelle & Cumano, Ana, eds. ( 2006 ). Hematopoietic stem cell development. Springer. ISBN 978 - 0 - 306 - 47872 - 7. CS1 maint : Uses editors parameter ( link ) External links Scholia has a topic profile for Haematopoiesis. Hematopoietic cell lineage in KEGG Hematopoiesis and bone marrow histology Immunology : lymphocytic adaptive immune system and complement Lymphoid Antigens Antigen Superantigen Allergen Hapten Epitope Linear Conformational Mimotope Antigen presentation / Professional APCs : Dendritic cell Macrophage B cell Immunogen Antibodies Antibody Monoclonal antibodies Polyclonal antibodies Autoantibody Microantibody Polyclonal B cell response Allotype Isotype Idiotype Immune complex Paratope Immunity vs. tolerance action : Immunity Autoimmunity Alloimmunity Allergy Hypersensitivity Inflammation Cross-reactivity inaction : Tolerance Central Peripheral Clonal anergy Clonal deletion Tolerance in pregnancy Immunodeficiency Immunogenetics Affinity maturation Somatic hypermutation Clonal selection V ( D ) J recombination Junctional diversity Immunoglobulin class switching MHC / HLA Lymphocytes Cellular T cell Humoral B cell NK cell Substances Cytokines Opsonin Cytolysin Organs of the lymphatic system Primary organs Bone marrow Hematopoietic stem cell Thymus Hassall 's corpuscles Secondary organs Spleen Structure Hilum Trabeculae Red pulp Cords of Billroth Marginal zone White pulp Periarteriolar lymphoid sheaths Germinal center Blood flow Trabecular arteries Trabecular veins Tonsils Palatine Lingual Pharyngeal Tubal Tonsillar crypts Waldeyer 's tonsillar ring Lymph nodes Lymphatic vessel T cells High endothelial venules B cells Germinal center Mantle zone Marginal zone MALT GALT Peyer 's patch Germinal center Myeloid physiology Hematopoiesis Myelopoiesis ( CFU - GEMM ) CFU - GM Granulopoiesis Myeloblast Promyelocyte Myelocyte Metamyelocyte Band cell Monocytopoiesis Monoblast Promonocyte MEP Thrombopoiesis Megakaryoblast Promegakaryocyte Erythropoiesis Proerythroblast Normoblast Reticulocyte General Extramedullary hematopoiesis Hemostasis Coagulation Fibrinolysis Clot retraction Platelet adhesiveness Other Erythrocyte aggregation Cell signaling : cytokines By family Chemokine CCL CCL1 CCL2 / MCP1 CCL3 / MIP1α CCL4 / MIP1β CCL5 / RANTES CCL6 CCL7 CCL8 CCL9 CCL11 CCL12 CCL13 CCL14 CCL15 CCL16 CCL17 CCL18 / PARC / DCCK1 / AMAC1 / MIP4 CCL19 CCL20 CCL21 CCL22 CCL23 CCL24 CCL25 CCL26 CCL27 CCL28 CXCL CXCL1 / KC CXCL2 CXCL3 CXCL4 CXCL5 CXCL6 CXCL7 CXCL8 / IL8 CXCL9 CXCL10 CXCL11 CXCL12 CXCL13 CXCL14 CXCL15 CXCL16 CXCL17 CX3CL CX3CL1 XCL XCL1 XCL2 TNF TNFA Lymphotoxin TNFB / LTA TNFC / LTB TNFSF4 TNFSF5 / CD40LG TNFSF6 TNFSF7 TNFSF8 TNFSF9 TNFSF10 TNFSF11 TNFSF13 TNFSF13B EDA Interleukin Type I ( grouped by receptor subunit ) γ chain IL2 / IL15 IL4 / IL13 IL7 IL9 IL21 β chain IL3 IL5 GMCSF IL6 like / gp130 IL6 IL11 IL27 IL30 IL31 + non IL OSM LIF CNTF CTF1 IL12 family / IL12RB1 IL12 IL23 IL27 IL35 Other IL14 IL16 IL32 IL34 Type II IL10 family IL10 / IL22 IL19 IL20 IL24 IL26 Interferon type III IL28 / IFNL2 + 3 IL29 / IFNL1 Interferon IFNA1 IFNA2 IFNA4 IFNA5 IFNA6 IFNA7 IFNA8 IFNA10 IFNA13 IFNA14 IFNA16 IFNA17 IFNA21 IFNB1 IFNK IFNW1 II IFNG Ig superfamily IL1 family : IL1A / IL1F1 IL1B / IL1F2 1Ra / IL1F3 IL1F5 IL1F6 IL1F7 IL1F8 IL1F9 IL1F10 33 / IL1F11 18 / IL1G IL17 family IL17 / IL25 ( IL17A ) Other Hematopoietic KITLG Colony - stimulating factor SPP1 MIF By function / cell proinflammatory cytokine IL1 TNFA Monokine Lymphokine IFNγ TNFβ IL4 IL5 IL6 IL10 IL13 Retrieved from `` https://en.wikipedia.org/w/index.php?title=Haematopoiesis&oldid=864242105 '' Categories : Hematopoiesis Histology Hidden categories : CS1 maint : Extra text : authors list CS1 maint : Uses editors parameter Talk Contents About Wikipedia Bosanski Català Čeština Deutsch Español Euskara Français Galego गोंयची कोंकणी / Gõychi Konknni 한국어 Հայերեն Bahasa Indonesia Italiano Қазақша Кыргызча Latina Lietuvių Magyar Македонски Nederlands پښتو Polski Português Română Русский Simple English Slovenčina Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska Türkçe Українська اردو 中文 27 more Edit links This page was last edited on 16 October 2018, at 00 : 55 ( UTC ). 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Question: where does myeloid hemopoiesis take place in adults
Answer: in the medulla of the bone (bone marrow)