Hematopoiesis maturation
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
As a stem cell matures it undergoes changes in gene expression that determines a specific cell type. Location is an important factor determining maturation. Growth factors influencing the signal transduction of various pathways altering transcription determining the different lineages of cells present.
Maturation
As a stem cell matures it undergoes changes in gene expression (the extent by which a gene exerts influence on its target changes) that limit the cell types that it can become and move it closer to a specific cell type. 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 its final choice of cell type and further limits its potential cell type until it is fully differentiated. This process is usually presented as a dendrogram or decision tree, which starts with a stem cell at the single starting point, and branches for the major lineages that branch into intermediate semi-differentiated cell types, and eventually, to fully differentiated cells.
Determination
It seems like it's the location of blood cells that makes the cell determination and not vice versa (i.e. e.g. that a hematopoietic stem cell determined to differentiate into a specific cell type would end up at a destined location). For instance, the thymus provides an environment for thymocytes to differentiate into a variety of different functional T cells.
For the stem cells and other undifferentiated blood cells in the bone marrow, the determination is generally explained by the determinism theory of hematopoiesis, saying that colony stimulating factors and other factors of the hematopoietic microenvironment determine the cells to follow a certain path of cell differentiation. This is the classical way of describing hematopoiesis. In fact, however, it is not really true. The ability of the bone marrow to regulate the quantity of different cell types to be produced is more accurately explained by a stochastic theory: Undifferentiated blood cells are determined to specific cell types by randomness. The hematopoietic microenvironment avails some of the cells to survive and some, on the other hand, to perform apoptosis. By regulating this balance between different cell types, the bone marrow can alter the quantity of different cells to ultimately be produced.
Haematopoietic Growth Factors
Red and white blood cell production is regulated with great precision in healthy humans, and the production of granulocytes is rapidly increased during infection. The proliferation and self-renewal of these cells depend on stem cell factor (SCF). Glycoprotein growth factors regulate the proliferation and maturation of the cells that enter the blood from the marrow, and cause cells in one or more committed cell lines to proliferate and mature. Three more factors which stimulate the production of committed stem cells are called colony-stimulating factors (CSFs) and include granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF) and macrophage CSF (M-CSF). These stimulate a lot of granulocyte formation. They are active on either progenitor cells or end product cells.
Erythropoietin is required for a myeloid progenitor cell to become an erythrocyte. [1] On the other hand, thrombopoietin makes myeloid progenitor cells differentiate to megakaryocytes (thrombocyte-forming cells).[1]
Examples of cytokines and the blood cells they give rise to, is shown in the picture below.
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Transcription Factors
Growth factors initiate signal transduction pathways, altering transcription factors, that, in turn activate genes that determines the differentiation of blood cells.
The early committed progenitors express low levels of transcription factors that may commit them to discrete cell lineages. Which cell lineage is selected for differentiation may depend both on chance and on the external signals received by progenitor cells. Several transcription factors have been isolated that regulate differentiation along the major cell lineages. For instance, PU.1 commits cells to the myeloid lineage whereas GATA-1 has an essential role in erythropoietic and megakaryocytic differentiation.
Extramedullary hematopoiesis in a thalassemia patient
