Cancer Stem Cells Theories and Practice by Stanley Shostak (Ed.)

By Stanley Shostak (Ed.)

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After pluripotency has been induced as depicted in the previous panels, the cells can be redirected towards new fates with the help of external of internal stimuli (cue nº 3). F) Tumorigenesis. An oncogenic hit (cue nº 2), hitting the right cellular intermediate with the right strength and angle sends the cell down to a new developmental program that will lead to the development of a tumour. According to this view, many of the second hits in tumorigenesis (nº 3, 4, 5) are already implicit given the first hit and the nature of the cell.

2006). These immature B cells leave the bone marrow and travel to the peripheral lymphoid organs where they become mature B cells (Hardy and Hayakawa, 2001). However, mature B cells in the periphery are not in fact, regardless of their name, the last differentiation stage of their lineage, because they are in fact waiting for an external signal (the antigen recognition) to experience the terminal differentiation process that will result in the generation of antibody-producing plasma cells. So, in response to T cell-dependent antigens, a dedicated structure, the germinal centre (GC) is formed, where B cells undergo several cycles of proliferation, somatic hypermutation, immunoglobulin class switching and selection.

Mature B cells and plasma cells have very different gene expression programs, which are controlled in a mutually exclusive manner by Pax5 and Blimp1, respectively. , 2002). , 2006). , 2006). But, since these genes are not compatible with B cell development or function they must be silenced to maintain B cell identity. However, as they will be required for terminal differentiation into plasma cells, they cannot be irreversibly repressed in B cells by stable epigenetic modifications. The molecular mechanism underlying this versatility is based on the function of Pax5: first, it preserves B cell identity, and afterwards it allows for a simple mechanism (repression of Pax5) of eliminating this identity when reprogramming becomes necessary to generate a plasma cell.

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