Long non-coding RNA contributes to direct conversion reprogramming

Over the last years, research led lncRNAs to go from transcriptional noise to important regulators of gene expression, being now known their association with many regulatory pathways by a wide set of mechanisms. Some of these RNAs play very important roles in cell differentiation, given their differential and temporal expression during tissue and organismal development. The discovery that terminally differentiated cells could revert to pluripotency or be redirected to multipotent progenitors of different lineages through forced expression of a specific onset of genes opened the way for direct conversion studies. The fact that various lncRNAs have been associated with differentiation, pluripotency and cancer indicates that these molecules might be useful tools in direct conversion. Manipulation of lncRNA expression during cell reprogramming could provide aid in overcoming current protocol limitations as the tumorigenic potential of iPSCs, low efficiencies and aging related epigenetic resistance. LncRNAs with influence in cell character transitions such as epithelial-mesenchymal transition (EMT) or mesenchymal-epithelial transition (MET) could contribute to direct conversion reprograming, as could lncRNAs that are specifically expressed in the reprogramming target cell line. We herein present two lncRNAs with the mentioned characteristics, Zeb2NAT and Pnky, respectively, as potential targets for improving fibroblast direct conversion reprogramming to multipotent hematopoietic and neural progenitors with a single pluripotency transcription factor (TF). Downregulation of Zeb2Nat during direct conversion seems to impair reprogramming efficiency, however if upregulating this lncRNA will have an improving effect is still under study. Getting unlimited patient-specific progenitor cells of different lineages from more accessible sources presents an enormous medical issue.