In the course of differentiation, in the overwhelming majority of cases, the cell genotype remains unchanged. However, tissue differences are inherited during cell reproduction (histiotypic growth). This means that the effects of determining influences are as a rule totally or almost totally irreversible, and hence only de-differentiation and not de-determination can take place. There is no return to a state from which different ways of development may be chosen.
Nuclear changes leading to stable differences in the rate of synthesis of many individual proteins between tissues (which we shall call epigenomic changes) have been little studied. Although these changes might reflect an inherited pattern of gene repression, neither the mechanism of gene repression in somatic cells nor that of the maintenance of repressed and de-repressed states during multiplication are known.
One of the main obstacles to the study of epigenomic variability is the lack of methods for defining simple tissue differences in the synthesis of individual proteins.
Gliomatosis peritonei as a natural experiment in tissue differentiation
