Differentiation programs

Although we will stick to the IL-6 gene, it should be mentioned at the side that two other RNA polymerases exist in mammalian cells responsible for the synthesis of RNA molecules, which are not translated into proteins ribosomal (rRNA), transfer (tRNA), small nuclear (snRNA), small nucleolar (snoRNA), and some of the recently discovered microRNAs and piRNAs. These RNA molecules act in the process of translation and mRNA turnover. Micro and piRNAs are probably extremely important in the definition of stem cells and of differentiation programs. Some of them are synthesized by RNA polymerase II. 

What is special about the testis that requires the absence of the circadian clock so pervasive in other tissues The testis has a number of characteristics, which make it quite different from other tissues. The testis contains spermatogenic cells that perform a constant and complex cell differentiation program where reductive cell divisions occur. It may be that the complex pattern of gene expression engendered by the circadian clock leads to unfavourable interactions with the developmental process of paramount importance to the testis. Alternatively, the normal oscillation of clock gene expression may be distorted by other transcriptional regulators or co-activators which are only present in seminiferous tubules (Sassone-Corsi 2002). 

Ivanov, II, McKenzie BS,Zhou L,TadokoroCE, LepelleyA, Lafaille JJ,Cua DJ, Littman DR The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17-i-T helper cells. Cell 2006 126 1121-33. 

Kishida, M. and G.V. Callard. Distinct cytochrome P450 aromatase isoforms in zebrafish Danio rerio) brain and ovary are differentially programmed and estrogen regulated during early development. Endocrinology 142 740—750, 2001. 

The possibility that the CB2 receptor plays a role in the control of immune cell fate is supported by studies on the gene expression profile ofhuman promyelocytic cells, which show that receptor activation up-regulates genes involved in the cell differentiation program (Derocq et al. 2000). These data, together with reports of CB2-induced blockade of neutrophilic differentiation (Alberich Jorda et al. 2003) and changes in CB2 receptor expression during the differentiation and activation ofhuman B cells (Carayon et al. 1998) point to an involvement of the CB2 receptor in the control of immune cell maturation. 

Transcription factors are involved in the differentiation programs and in the activation processes of T lymphocytes and B lymphocytes in normal and neoplastic conditions. The availability of antibodies able to efficiently recognize these TFs in formalin-fixed paraffin embedded tissues represents a powerful tool in diagnostic hemato-pathology. 

Most of the TFs are localized in the nucleus and are seen in all or most of the cells with the same differentiation program or functional status. The following are key diagnostic TFs for B-cell immunohistology. A summary of B-cell TFs is in Table 6.1. 

Hinrichs CS et al. IL-2 and IL-21 confer opposing differentiation programs to CD8 -cells for adoptive immunotherapy. Blood 2008 111 5326-5333. 

Borjesson, D. L., Kobayashi, S. D., Whitney, A. R., Voyich, J. M., Argue, C. M., and DeLeo, F. R. (2005) Insights into pathogen immune evasion mechanisms Anaplasma phagocytophilum fails to induce an apoptosis differentiation program in human neutrophils. J. Immunol. 174, 6364-6372. 

Stem cells attracted significant attention in recent years, due to their enormous potential in regenerative medicine. Their capacity for endless self-renewal and plasticity makes them ideal tools for the treatment of a number of diseases. Unfortunately, the same qualities make them precursors for the development of cancer cells if their cell cycle control fails and/ or their differentiation programs go astray. Thus, cancer could be perceived as a disease of stem cells. 

Tightly linked with the realization of differentiation programs are the phenomena of (a) competence, i.e., the stage-restricted capability of cells to respond to particular signals by expression of distinct parts of their genetic material and of (b) determination, i.e, the commitment of cells to certain differentiation processes or programs by prior changes of their chemical composition. 

Usually the response of the target cells depends on their state of differentiation (competence). Since secondary metabolism is integrated into differentiation programs, the phase during which secondary metabolism may be influenced is not necessarily linked directly to the stage of secondary product formation. 

The rate of secondary product formation may be influenced by many different mutations. In most cases they act indirectly, e.g., by influencing the flow of precursors, cosubstrate biosynthesis, or differentiation programs. Mutations in the genetic material directly controlling the expression of secondary metabolism are rare (A 2.1). The genetic regulation of secondary product formation in most organisms is therefore still unknown. 

---