Generation of numerous functional somatic cells in a practical and effective manner is a major challenge in the field of regenerative medicine. In vitro induction of cell plasticity and the expansion of its capabilities by direct reprogramming has great promise for meeting this challenge. In addition to the potent genetic manipulation of transcription factors (TFs), integration-free approaches for the direct conversion of somatic cell fate have gained considerable interest in recent years; including synthetic RNAs, cell membrane–permeable proteins, episomal plasmids, and chemical compounds. Each single method has its own unique advantages and limitations. Recently, several chemical compounds have been shown to synergistically improve the TFs-mediated cell reprogramming with enhanced efficiency and functions, providing us with critical insight into the potential of combined methods in direct reprogramming of somatic cells.
The aim of this collection is to (1) share the achievements in direct reprogramming of functional somatic cell types using new methods; (2) find the limitations in the current reprogramming methods and elucidate the mechanisms; (3) provide evidence that combined methods may further enhance the reprogramming efficiency, cell functions, or in vivo repopulation capability; (4) compare, optimize, and finally standardize the current reprogramming methods targeting specific cell types (such as neurons, cardiomyocytes, hepatocytes, pancreatic β cells, melanocytes and their progenitors); (5) identify how the TFs, RNAs, proteins, plasmids, or chemical compounds individually or synergistically regulate the cell signal pathways and map the reprogramming networks towards cell fate conversion; and (6) explore the induction microenvironment under different culture patterns such as 3D spheroids and multicellular organoids.