A further factor that may be neglected is the clarification of metabolic fluxes caused by exogenous reprogramming metabolites.
It has been suggested that the commonly observed low developmental efficiency of NT embryos may not be largely due to nuclear reprogramming during early embryo development but potentially caused by abnormal gene reprogramming during postimplantation feto-placental development [ 20].
This suggests that AMPK and NUAK1 normally help to protect these cells against the stresses caused by the metabolic reprogramming that accompanies c-Myc over-expression.
However, clonal regenerant animals display variant phenotypes caused by defective epigenetic reprogramming of gene expression [ 2], and clonal regenerant plants exhibit poorly understood heritable phenotypic ("somaclonal") variation [ 4 7].
For example, cancer cells react to the hypoxia caused by anti-angiogenic signals by reprogramming their metabolism, thus increasing the uptake of glucose to sustain energy production through glycolysis.
Consistent with this, there is growing evidence from studies with a number of drugs, which are currently in clinical trials [ 52], that epigenetic changes can bypass the genetic alterations caused by malignancy and reprogram gene expression by changing the epigenetic state of the cells.
As discussed in more detail in the following sections, most of these alterations caused by genetic factors or epigenetic reprogramming affected AECs and provoked an exacerbated fibrotic response without inflammation or with an inflammatory response in animal models, similar to that observed in wild-type littermates.
It was reported that iPS cells are immunogenic post transplantation, which may be caused by mutations during the reprogramming and long time in vitro culture process.
In this research, we have conducted a study that has focused on the genome-wide changes of several relevant histone modifications associated with the major transcriptional reprogramming caused by osmotic stress.
By contrast, there may be a more general reprogramming caused by EDCs, such that exposed individuals and their offspring have altered responses to environmental (proximate) stimuli that go beyond a single system (e.g., estrogenic EDCs) and affect a broader array of responses, including stress responsiveness, as we use as an example below.
These changes are caused by epigenetic and/or genetic events that "reprogram" the regulation of gene transcription [ 4].
