Stress as a fundamental theme in cell plasticity

• Cellular plasticity is widespread in non-mammalian as well as mammalian cells.
• Dedifferentiation and transdifferentiation events account for such plastic events.
• Environmental factors dictate plasticity potential of mature cells.
• The cellular neighborhood provides restrictions for plastic events.
• Stress leading to cell isolation might lift such restrictions, enabling plasticity.

Over a decade of intensive investigation of the possible plasticity of mammalian cells has eventually substantiated that mammalian species are endowed with a remarkable capacity to change mature cell fates. We review below the evidence for the occurrence of processes such as dedifferentiation and transdifferentiation within mammalian tissues in vivo, and in cells removed from their protective microenvironment and seeded in culture under conditions poorly resembling their physiological state in situ. Overall, these studies point to one major conclusion: stressful conditions, whether due to in vivo tissue damage or otherwise to isolation of cells from their in vivo restrictive niches, lead to extreme fate changes. Some examples of dedifferentiation are discussed in detail showing that rare cells within the population tend to turn back into less mature ones due to severe cell damage. It is proposed that cell stress, mechanistically sensed by isolation from neighboring cells, leads to dedifferentiation, in an attempt to build a new stem cell reservoir for subsequent regeneration of the damaged tissue. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity.