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Part I different fields# _& y! o9 w: s' Q5 U2 _. P7 z
Many of the terms commonly used have different meanings for different authors in different fields (for example, researchers working in different model organisms), in some
( x9 v% j+ @2 H6 a6 J. g2 D7 Kcases more restrictive, in some more wide-ranging. & p( w. l: Z$ c- _( f8 G8 ?8 r! }
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I suggest that we use the following terminology :
2 p: ]1 s7 [8 X' H, ]4 ?, ?5 @- “Dedifferentiation”: the mechanism by which the normal developmental program is reverted in such a way that differentiated cells give rise to more plastic, earlier progenitors.
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- “Cancer Stem Cells” (CSCs): the cells responsible for the maintenance, propagation, metastasis and relapse of tumors. They posses self-renewal and differentiation capabilities and can give rise to all the cellular types that compose the tumor mass. Also named cancer-maintaining-cells.
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, J3 f" G) P" r4 Y1 v3 R7 ^- “Transdifferentiation” designs the direct conversion (reprogramming) of a differentiated cell type into another different mature cell, without the need of
8 ^4 n" u/ t5 [8 h# b% Ldedifferentiating to earlier developmental stages; it usually involves the passage through cellular intermediates that are non-physiological and share markers that are ( j- G" v) A) ^7 D& D
normally mutually exclusive, corresponding to the initiating and the final cell. As we will discuss later, induced pluripotency would be a particular case of transdifferentiation, rather than being a dedifferentiation process, due to the existence of those non-physiological intermediates.
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- “Commitment”: the point of no return in physiological development, where the cell irreversibly enters a specific differentiation program. For a stem cell, it implies the loss of self-renewal.
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- “Epigenetic”: the inheritance of patterns of gene expression, without affecting the genetic code itself. In other words, the inheritance that is not codified in the DNA sequence. From the molecular point of view, it designs all the chromatin modifications that establish (and determine the propagation of) the different possible patterns of - B* R* R; {8 J2 o
gene expression of a given, unique genome. ' v- U7 R5 l6 t' \ N/ B
; k0 v+ d8 ]. N- P a# R, |: o- “Reprogramming”: from the cellular point of view, the natural or experimentally-induced alteration of the differentiation program of a given cell. From the molecular point of view, all the molecular changes (i.e., epigenetic) that take place in a cell that is changing its identity. Dedifferentiation and transdifferentiation are types of
& p; ~/ b0 v! c" b- L; v7 E; a- yreprogramming, usually experimentally-induced. Oncogenesis is also a form of reprogramming, in this case one that spontaneously happens in nature.
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- “Cancer cell-of-origin”: the normal cell that first suffers the oncogenic hit and initiates the tumoral process. It is usually the one giving rise to the CSC. It can be either a differentiated cell or a stem/progenitor cell. |
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发表于 2011-6-22 21:07
发表于 2011-6-23 21:23
