Transdifferentiation of Fibroblasts by Defined Factors.

Cellular differentiation is usually considered to be an irreversible process during development due to robust lineage commitment. Feedback and feed-forward loops play a significant role in maintaining lineage-specific gene expression processes in various cell types, and, in turn, factors secreted by cells may regulate the homeostatic balance of these cycles during development and differentiation. The output of biological responses is controlled by such mechanisms in many regulatory pathways through gene networks involved in transcription, RNA metabolism, signal transduction, micromolecular synthesis, and degradation. The pluripotent stage during cellular conversion may be avoided through ectopic expression of lineage-specific factors. Lineage-specific transcription factors produced during development may strengthen cell type-specific gene expression patterns. Cellular phenotypes are further stabilized by epigenetic modifications. This reprogramming approach could have important implications for disease modeling and regenerative and personalized medicine.