The roles of non-coding RNAs in the self-renewal and differentiation of pluripotent stem cells

There are thousands of cell types in the animal body, many of which can be derived from embryonic stem cells (ES cells), a pluripotent cell type that thrive in cell culture condition. ES cells differentiate into various cell type in a tissue culture dish in response to different growth factor/cytokine treatment, which can be transplanted back into animals for regenerative medicine application. In recent years, scientists have generated another type of pluripotent stem cell population, designated as induced pluripotent stem cells (iPS cells). These iPS cells are derived from adult cell types, and capable of differentiating into a variety of cell types in a tissue culture dish. Both ES cells and iPS cells not only provide a unique paradigm to study early mammalian development, but also hold great promise for regenerative medicine. Therefore, understanding the molecular network that regulate stem cell maintenance and stem cell differentiation of these cell types are very important for their application in regenerative medicine. In the studies we proposed, we will examine a novel class of gene regulators for their functions to maintain the stem cell population, as well as to trigger their differentiation into specific lineages. The focus of our studies is non-coding RNAs, which are RNA molecules that do not have capacity to encode proteins. Among the best studied non-coding RNAs are the microRNAs, which are small RNA molecules that are potent regulator for gene expression. These small RNAs often have the capacity to each regulate hundred of genes, therefore, regulating diverse developmental processes and physiological processes. If the biogenesis of these small RNAs are removed, stem cells exhibit multiple defects both in the tissue culture dish and in animal development. In this proposal, we aim to investigate the roles of non-coding RNAs in the regulation of stem cell maintenance and differentiation, and to identify novel non-coding RNA regulators that may impact stem cell biology. It is worth noting that RNA therapies, particularly those using synthetic small RNAs or their inhibitors, bypass the need for conventional gene therapy, and provide great promise for clinical application. The methods to delivery small RNAs into the cells and animals have been improved significantly over the past decade, and it is very likely that small RNAs and their inhibitors will be soon utilized for therapeutic applications. Therefore, our proposed research will generate exciting findings to stem cell biology and may lead to the development of novel diagnostic markers and therapeutic approaches for regenerative medicine.