Cellular differentiation is the process that cells of the same origin gradually produce cell groups with different morphological structures and functional characteristics. The essence of cell differentiation is the selective expression of the genome in time and space. By turning on or off the expression of different genes, the final signature protein is produced. In general, the cell differentiation process is irreversible. All cells presumably derive from stem cells and obtain their functions as they mature, such as muscle cell, blood cell, nerve cell and cardiac cell (Figure 1). Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals.
Figure 1. The diagram of cell differentiation
Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms. Regulation of differentiation has remained a matter of serious investigation during past four decades. Several studies have demonstrated that cytokines and growth factors can be used in in vitro assays to stimulate differentiation of ESCs and iPSCs toward ectoderm, endoderm, and mesoderm derivatives, and germ cells. Moreover, accumulating evidence have shown bone marrow progenitors differentiate into many subsets of innate effector cells after receiving instructional signals often provided by cytokines, such as IL-3, IL-4, IL-5 and IL10. Generally speaking, cytokines differ from differentiation of different types of cells. In this article, we introduce the cytokines of several common cells differentiation.
Cytokines and Native CD4+ Helper Cells Differentiation
As mention on the article named T Cell Cytokines, CD4+ helper cells, also known as Th cells, can differentiate into several subsets of Th cells with different cytokines stimulation. The latest subsets of Th cells differentiation include Th1, Th2, Th9, Th17, Th22 and Tfh cell. Th1 cells are differentiated from Th cells with IL-12 and IFNγ stimulation. IL4 can induce Th cells to differentiate into Th2 cells alone. However, if IL-4 is together with TGFβ, the Th cells will differentiate into Th9 cells. And the differentiation cytokines of Th17 include IL-1, IL-6, IL-23 and TGFβ. Furthermore, Th cells differentiate into Tfh under the IL-6 stimulation only. But, if IL-6 is together with TNFɑ, the Th cells will differentiate into Th22 cells.
Cytokines and Plasma Cells Differentiation
Plasma cells, also known as plasma B cells, are white blood cells that originate in the bone marrow. Plasma cells can secrete large quantities of proteins named antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen, where they initiate its neutralization. B cells differentiate into plasma cells that produce antibody under cytokine stimulation, including IFNγ, TGFβ, IL4, IL-2 and IL-5. Among of them, IFNγ induces B cells to differentiate into the plasma cells secreting IgG2a or IgG3 antibody; the plasma cells differentiated by IFNγ stimulation can secret IgA or IgG2b antibody; the plasma cells differentiated by IL-4 stimulation can secret IgE or IgG1 antibody; and the plasma cells differentiated by IL-2, IL-4 and IL-5 stimulation can secret IgM antibody.
Cytokines and Other Cells Differentiation
Several cytokines have been shown to regulate mast cell differentiation, survival and function. SCF and IL-3 are critical factors for mast cell development and both cytokines can activate STAT5. IL-5 is a critical factor for eosinophil differentiation, activation, survival and recruitment to the sites of inflammation. IL-10, a suppressive cytokine produced mainly by regulatory T cells, inhibits T cell proliferation and enhances B differentiation. TGF-β, IL-8 and Flt-3 stimulate self-renewal of hematopoietic stem cells. M-CSF only promotes macrophage lineage survival, proliferation, differentiation and activation. G-CSF is required for differentiation, proliferation and activation of neutrophils. EPO stimulates the proliferation and differentiation of erythroid progenitor cells to red blood cells.