Differentiation, cellular

In an extensive series of experiments it could be demonstrated that bones, cartilage and fibrous tissues are produced from similar fibroblasts501 503. Furthermore, transformation of one skeletal tissue into another one in either direction is possible. Thus, the former concept on the fixity of cell types which says that once a cell had differentiated into myoblast, chondroblast or osteoblast it could only produce muscle fiber, cartilage or bone, respectively, had to be revised. 

The fact that cartilage, bone and fibrous tissue generating cells are readily inter-changable indicates that the individual progenitor cells share the same genetic information. The question thus comes up what factor or cofactors determine the direction of cellular flow  

---

Retinoids are needed for cellular differentiation and skin growth. Some retinoids even exert a prophylactic effect on preneoplastic and malignant skin lesions. Fenretlnide (54) is somewhat more selective and less toxic than retinyl acetate (vitamin A acetate) for this purpose. It is synthesized by reaction of all trans-retinoic acid (53), via its acid chloride, with g-aminophe-nol to give ester 54 (13). 

This model was first introduced by Kauffman [kauff69] in a study of cellular differentiation in a biological system (binary sites were interpreted as elements of an ensemble of genes switching on and off according to some set of random rules). Since its original conception, however, related models have found wide application in an... 

Decitabine (5-aza-deoxycytosine) is an analog of the nucleoside 2 -deoxycytidine. It is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and by inhibition of the enzyme DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. DNA hypomethylation is achieved at concentrations below those required to significantly inhibit DNA synthesis, which may promote restoration of function to genes associated with control of cellular differentiation and proliferation. Cytotoxicity in rapidly dividing cells may also result from covalent adducts between DNA methyltransferase and decitabine. 

The predominant cell type in the pancreatic islets of Langerhans. The main secretory product of the (3 -cell is the peptide hormone insulin which has vital actions for the control of nutrient homeostasis and cellular differentiation. 

While activation of HSFl and HSF2 results in the increased expression of HS genes, recent studies indicate that there are distinct differences between these transcription factors. As noted previously, HSFl is the heat-inducible form of the HS factors, whereas HSF2 is activated by hemin (Sistonen et al., 1992). This observation has indicated a possible role of HSF2 in cellular differentiation. It also indicates that the activation domains of the two transcription factors are quite different. Presumably the DNA binding properties of the two transcription factors are similar, but recent experiments indicate otherwise (Kroger and Morimoto,... 

While much has been learned about the HS response, our understanding is still incomplete. Why, for instance, are there multiple HS transcription factors Are some of these factors utilized during development and cellular differentiation ... 

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

In mammals, as in yeast, several different metallothionein isoforms are known, each with a particular tissue distribution (Vasak and Hasler, 2000). Their synthesis is regulated at the level of transcription not only by copper (as well as the other divalent metal ions cadmium, mercury and zinc) but also by hormones, notably steroid hormones, that affect cellular differentiation. Intracellular copper accumulates in metallothionein in copper overload diseases, such as Wilson s disease, forming two distinct molecular forms one with 12 Cu(I) equivalents bound, in which all 20 thiolate ligands of the protein participate in metal binding the other with eight Cu(I)/ metallothionein a molecules, with between 12-14 cysteines involved in Cu(I) coordination (Pountney et ah, 1994). Although the role of specific metallothionein isoforms in zinc homeostasis and apoptosis is established, its primary function in copper metabolism remains enigmatic (Vasak and Hasler, 2000). 

Flaim CJ, Chien S, Bhatia SN (2005) An extracellular matrix microarray for probing cellular differentiation. Nat Methods 2 119-125... 

A closely related challenge is the design of materials that interact with cells or living tissues to promote desired biological responses. Such responses might be cell attachment, cellular differentiation and organization into functional tissue, or promotion of in-growth of bone into an artificial prosthesis such as an artificial hip. 

The ability of interferons (especially type I interferons) to induce an antiviral state is unlikely to be solely dependent upon the enzymatic mechanisms discussed above. Furthermore the 2 -5 A synthetase and eIF-2a kinase systems may play important roles in mediating additional interferon actions. The ability of such systems to stall protein synthesis in cells may play a role in interferon-induced alterations of cellular differentiation or cell cycle progression. They may also be involved in mediating interferon-induced anti-proliferative effects on various transformed cells. 

Mechanisms by which copper deficiency results in neutropenia, with emphasis on the process of cellular differentiation and the viability of neutrophils in blood and marrow (Percival 1995)... 

The adult skeleton is periodically remodeled by transitory anatomic structures that contain juxtaposed osteoclast and osteoblast teams and that replace old bone with new bone. The purpose of this remodeling is both to prevent bone aging and repair the damage that occurs as well as to guarantee a contribution of minerals, especially calcium, to body cells for their correct function. In the last few years, due mainly to the research in molecular biology and cellular differentiation and to studies of genetically manipulated mice, it has been possible to discover many aspects both of the cellular and molecular bases of this bone remodeling as well as of the differentiation and function of the two main implied cell types osteoblasts and osteoclasts. 

In the ways described above, only the genes required at a given moment are expressed. This not only helps to conserve the energy of the cell, but also is critical for correct cellular differentiation, tissue pattern formation and formation of the body plan. 

Involved in the control of cellular growth is c-fos, whose expression is transiently activated by certain growth factors and tumour promoters and may also be activated during cellular differentiation and by cAMP. In neutrophils, c-fos mRNA is expressed at low rates, but transcripts are greatly increased by fMet-Leu-Phe (2-50 nM). This expression is transient (peak-... 

The discovery of TNTs may end up challenging the established cell theory concept of a cell as the primary unit of life in animals, if future studies can reveal a role of TNT-mediated communication in fundamental cellular processes. In the plant kingdom the multicellular organism is already considered the primary unit of life, driven by the role of plasmodesmata, cytoplasmic channels interconnecting plant cells, in processes such as cellular differentiation and development (reviewed in Baluska et al. (2004)). 

H.E. Meyer Zu Schwabedissen, M. Grube, B. Heydrich, K. Linnemann, C. Fusch, H.K. Kroemer, and G. Jedlitschky. Expression, localization, and function of MRP5 (ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts Effects of gestational age and cellular differentiation. Am J Pathol. 166 39 18 (2005). 

Isfort, R.J., Cody, D.B., Doerson, C., Kerckaert, G.A., and LeBoeuf, R.A., Alterations in cellular differentiation, mitogenesis, cytoskeleton and growth characteristics during Syrian hamster embryo cell multistep in vitro transformation, Int. J. Cancer, 59, 114, 1994. 

Butler LM, Webb Y, Agus DB, Higgins B, Tolentino TR, Kutko MC, LaQuaglia MP, Drobnjak M, Cordon-Cardo C, Scher HI, Breslow R, Richon VM, Rifkind RA, Marks PA (2001) Inhibition of transformed cell growth and induction of cellular differentiation by pyroxamide, an inhibitor of histone deacetylase. Clin Cancer Res 7(4) 962-970... 

McLaren EH, Svendsen CN, Van der Meide P, Joly E. 2001. Analysis of neural stem cells by flow cytometry cellular differentiation modifies patterns of MHC expression. J Neuroimmunol 112 35-46. 

Ogas, J., Cheng, J.C., Sung, Z.R., and Somerville, C. (1997) Cellular differentiation regulated by gibberellin in the Arabidopsis thaliana pickle mutant. Science 277, 91-94. 

This reversible HDAC inhibitor has potency in low nanomolar ranges. ° TSA induces cellular differentiation, apoptosis and growth factor unresponsiveness when administered under regimental dosing and not under single dose administration. However, TSA showed poor results in clinical trials, likely due to a combination of poor biodistribu-fion and fast metabolism. 

Beppu T, Secondary metabolites as chemical signals for cellular differentiation,... 

---