The establishment and maintenance of mitotically and meitotically stable -epigenetic- gene expression patterns is paramount for cell proliferation and differentiation. Long non-coding RNAs (ncRNAs) have emerged as important regulators of epigenetic gene expression, in particular epigenetic gene silencing. NcRNAs have been associated with imprinting, gene dosage compensation, gene silencing and metastasis. NcRNAs silence gene expression by recruiting epigenetic repressors of the Polycomb group family to target genes. However, the functional importance of ncRNAs in stem cell biology remains unknown.
This project is aimed at the dissection of the role and function of ncRNAs in stem cell differentiation. During the funding period, we have focused on the functional characterization of one ncRNA. The ncRNA is transcribed in differentiating embryonic stem cells (ESCs) and facilitates activation of Hox genes. Hox genes are key regulators of cell differentiation and establish the developmental fate of cells. Destruction of Mistral through RNAi attenuates the differentiation of ESCs. Collectively, our results uncover a role for the ncRNAin epigenetic activation of gene expression and stem cell differentiation and identify ncRNAs as important regulators of stem cell differentiation. The obtained results establish a foundation for the development of novel tools and assays that actively control the differentiation of stem cells and direct the differentiation of stem cells into a desired cell type.