Terminal differentiation

In the skin, ENaC is expressed in keratinocytes of the epidermis and in hair follicles. It could play a role in terminal differentiation by modulating keratinocyte calcium signaling. The skin expresses MR, GR, and 11 3HSD2, but the role of aldosterone and glucocorticoids on ENaC activity and keratinocyte differentiation is not yet understood. 

All mature blood cells arise from primitive hematopoietic cells in the bone marrow, the pluripotent stem cells. Approximately 0.1% of the nucleated cells of the bone marrow are pluripotent stem cells and approximately 5% of these cells may be actively cycling at any one time. The stem cell pool maintains itself through a process of asymmetrical cell division when a stem cell divides, one daughter cell remains a stem cell and the other becomes a committed colony-forming cell (CFC). The proliferation and differentiation of CFCs are controlled by hematopoietic growth factors. The hematopoietic growth factors stimulate cell division, differentiation and maturation, and convert the dividing cells into a population of terminally differentiated functional cells. 

In spite of the above-mentioned similarities between basophils and mast cells, they differ in many other aspects [1,2]. Basophils complete their differentiation within the bone marrow, and mature basophils circulate in the peripheral blood and do not usually infiltrate into peripheral tissues unless inflammation takes place. Mast cells originate from hematopoietic cells in the bone marrow as do basophils, but they mature in peripheral tissues after their bone marrow-derived precursors enter the circulation and migrate into peripheral tissues. Mature mast cells reside in peripheral tissues and do not usually circulate in the peripheral blood. The lifespan of basophils is very short (several days), in contrast to that of mast cells (weeks to months). Basophils do not proliferate once they terminally differentiate whereas mature mast cells keep potential to expand in response to various stimuli. These differences between basophils and mast cells, including distinct anatomical localization, suggest their differential roles in vivo. 

All secondary cell walls develop from primary cell walls. Cells no longer grow once lignin is added to their wails. Lignification, which is a key step in the conversion of a primary cell wall into a secondary cell wall, results in terminal differentiation of the encased cell. Indeed, many cells with lignified walls die. The totipotency of plant cells is limited to cells enveloped in primary walls. 

HPV replicates in terminally differentiated squamous cells in the intermediate layers of the genital mucosa. Hence, these effects of the viral early region genes on DNA synthesis are critical for viral survival. Genital warts are the clinical manifestation of active viral replication and virion production at the infection site. 

Muehlinghaus G, Cigliano L, Huehn S, et al. Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells. Blood 2005 105 3965-3971. 

Figure 1. Hierarchy of control of gene expression. A total of about 50,000 to 100,000 genes are necessary to encode a mammal, most of which encode housekeeping, structural component, or terminal differentiation gene products. Transcription factor genes regulate expression of the lower-level genes and are in turn controlled by other upper-level transcription factors.

This mode of regulation seems appropriate to the ERTs since their cells are already terminally differentiated, and their primary function is to grow and provide a nutrient rich incubator for the undifferentiated neuroblasts and imaginal cells that eventually produce the reproductive adult. The response of these undifferentiated progenitor cells to food withdrawal is quite unlike that of the ERTs. Larval neuroblasts and imaginal disc cells continue to proliferate for many days after a larva is starved, and seem to complete their normal proliferation programs. In this instance the ERTs lose mass, presumably as they transfer stored nutrients to the developing nervous system and the discs. 

Edgar The larva is a fully functional animal made up of terminally differentiated cells, but its purpose is to be an incubator for these imaginal discs that make the fly. It has to bulk up on mass and it transfers this biomass to the discs as they grow. I think it is a really simple way for an organism that is already differentiated to grow. It is a sort of stripped-down cell cycle that can respond to nutrition. There is no need for those cells to proliferate. 

Most mammalian cell types develop from precursor cells that divide a limited number of times before they stop and terminally differentiate. In no case do we understand why the cells stop dividing when they do. The stopping mechanisms are important because they determine how many differentiated cells are produced and when differentiation begins. We have been studying the stopping mechanism in oligodendrocyte precursor cells (OPCs) isolated from the developing optic nerve of rats and mice. 

OPCs divide a limited number of times in the nerve and then terminally differentiate into postmitotic oligodendrocytes. The first OPCs stop dividing and differentiate on the day of birth (Miller et al 1985), and new ones do so over the next six weeks (Barres et al 1992). We have studied the mechanisms that control when the OPCs stop dividing and differentiate in culture and find that both cell-intrinsic programmes and extracellular signals are involved. 

Raff I think the timing mechanism may be similar in many cell lineages where precursors divide a limited number of times and then stop and terminally differentiate. The best evidence for this is that if you inactivate p27 there are more... 

Eajf Another big question is how cell-cycle withdrawal and terminal differentiation are coupled. 

Infection-induced cell cycle re-entry and suspension in G2/M occur early in infection and are likely to influence regulation of some of the other host cell effects (Jasmer, 1993). The earliest indication that 7. spiralis induces terminally differentiated skeletal muscle cells to re-enter the cell cycle came... 

Endo, T. and Nidal-Ginard, B. (1988) SV40 large T antigen induces reentry of terminally differentiated myotubes into the cell cycle. In Kedes, L.H. and Stockdale, F.E. (eds) Cellular and Molecular Biology of Muscle Development. Alan R. Liss, New York, pp. 95-104. 

Translation-competent ER membrane fractions can also be prepared from tissue culture cells. We recommend a terminally differentiated secretory suspension cell line, such as a plasmacytoma (e.g., J558L), which contains abundant levels of ER membrane. In this protocol, cells are collected by centrifugation (5 min, 500 x g) and resuspended in a homogenization buffer containing 10 mMKOAc, 10 mMK-HEPES, pH 7.5, 1.5 mMMg(OAc)2,... 

Uncommitted Migration Committed Terminally-differentiated Neural Crest Cell Determination Progenitors Derivatives... 

Bondy, G.S., and Pestka, J.J., Dietary exposure to the trichothecene vomitoxin (deoxyni-valenol) stimulates terminal differentiation of Peyer s patch B cells to la secreting plasma cells, Toxicol. Appl. Pharmacol., 108, 520, 1991. 

Aghajanian. G. K... Kuhar, M. J., and Roth, R. H. (1973) Serotonin-containing neuronal perikarya and terminals differential effects of p-chlorophenylalanine. Brain Res., 54 85-101. 

Plasma cells Secrete antibody terminally differentiated... 

At the corneal surface, two to four layers of polygonal, extremely flat, and terminally differentiated superficial cells can be found. The cell diameters are 40-60 /xm with about 2-6 /xm thickness. The corneal surface is populated with microvilli and microplicae, resulting in surface area enlargement. These structures are associated with the tear film. Superficial corneal epithelial cells are... 

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