This is an advanced topic
This is an area of active research since it illustrates the importance
of an understanding of the mechanisms of differentiation.
Two models of metaplasia or transdifferentiation exist.
At one extreme it might be that a given
differentiated cell type can convert directly
into another differentiated cell type.
An alternative view is that the apparent
conversion of one differentiated cell type by another is a consequence of re-specification
of a stem cell such that now its progeny have a different pattern of
gene expression (and hence differentiated state or phenotype) compared
with the normal.
It is a fact that, in general, the differentiated state of a cell is a
rather fixed and unchanging attribute. For example a skin cell does
not spontaneously convert into a neurone. However the fertilised
oocyte has total plasticity since its progeny can become all the different
cells of the adult body.
An increasing body of information shows that stem cells have a wide
potential array of progeny cells with different phenotypes. This is
usually quite restricted under normal physiological situations. For
example in the gastrointestinal tract there is evidence that all four
differentiated cell types of the colonic crypt epithelium (mucous cells,
absorptive cells, goblet cells and endocrine cells) can all derive from a
common precursor stem cells located at the base of the crypt.
What is clear is that we have a remarkably poor understanding of the
detailed mechanisms that determine regulated gene expression in the context
of differentiation.
Slack has proposed that metaplasia represent the
mammalian equivalent of homeotic mutations that occur in invertebrates and
allow (in development) the respecification of a developing body part due to
a mutation in master regulator genes. See for example his paper in the Lancet
in 1985 or a more
recent review.
Importantly this kind of complex area indicates
the inter-dependence of much of modern biology and medicine, such that to
understand pathological and clinical phenomena will require understanding of
basic biological issues such as stem cells, mechanisms of differentiation
and the like.
