The Functions of MicroRNAs and Long Non-coding RNAs in Embryonic and Induced Pluripotent Stem Cells

Embryonic stern cells （ESCs） and induced pluripotent stem cells （iPSCs） hold immense promise for regenerative medicine due to their abilities to self-renew and to differentiate into all cell types. This unique property is controlled by a complex interplay between transcriptional factors and epigenefic regulators. Recent research indicates that the epigenetic role of non-coding RNAs （ncRNAs） is an integral component of this regulatory network. This report will summarize findings that focus on two classes of regulatory ncRNAs, microRNAs （miRNAs） and long ncRNAs （lncRNAs）, in the induction, maintenance and directed differentiation of ESCs and iPSCs. Manipulating these two important types of ncRNAs would be crucial to unlock the therapeutic and research potential of pluripotent stem cells.

Pluripotency of Induced Pluripotent Stem Cells

Induced pluripotent stem （iPS） cells can be generated by forced expression of four pluripotency factors in somatic cells. This has received much attention in recent years since it may offer us a promising donor cell source for cell transplantation therapy. There has been great progress in iPS cell research in the past few years. However, several issues need to be further addressed in the near future before the clinical application of iPS cells, like the immunogenieity of iPS cells, the variability of differentiation potential and most importantly tumor formation of the iPS derivative cells. Here, we review recent progress in research into the pluripotency of iPS cells.

Induced Neural Stem Cells Generated from Rat Fibroblasts

The generation of induced tissue-specific stem cells has been hampered by the lack of well-established methods for the maintenance of pure tissue-specific stem cells like the ones we have for embryonic stem （ES） cell cultures. Using a cocktail of cytokines and small molecules, we dem- onstrate that primitive neural stem （NS） cells derived from mouse ES cells and rat embryos can be maintained. Furthermore, using the same set of cytokines and small molecules, we show that induced NS （iNS） cells can be generated from rat fibroblasts by forced expression of the transcrip- tional factors Oct4, Sox2 and c-Myc. The generation and long-term maintenance of iNS cells could have wide and momentous implications.

Cellular Reprogramming of Human Peripheral Blood Cells

Breakthroughs in cell fate conversion have made it possible to generate large quantities of patient-specific cells for regenerative medicine. Due to multiple advantages of peripheral blood cells over fibroblasts from skin biopsy, the use of blood mononuclear cells （MNCs） instead of skin fibroblasts will expedite reprogramming research and broaden the application of reprogramming technology. This review discusses current progress and challenges of generating induced pluripotent stem cells （iPSCs） from peripheral blood MNCs and of in vitro and in vivo conversion of blood cells into cells of therapeutic value, such as mesenchymal stem cells, neural cells and hepatocytes. An optimized design of lentiviral vectors is necessary to achieve high reprogramming efficiency of peripheral blood cells. More recently, non-integrating vectors such as Sendai virus and episomal vectors have been successfully employed in generating integration-free iPSCs and somatic stem cells.