Regulatory RNAs in stem cells
Long intergenic non-coding RNAs (lincRNAs) have emerged as novel regulators of fundamental biological processes. However, the vast majority of lincRNAs have not been functionally characterised and their role in the maintenance of adult stem cells has not been elucidated. To understand the physiological relevance of lincRNAs, scientists on the EU-funded project LINCRNA (The role of long intergenic non-coding RNA in intestina stem cells) set out to study the role of lincRNAs in the development of intestinal stem cells. The unique structure and vigorous self-renewing property of intestinal epithelium makes it one of the most accessible models for adult stem cell study. Scientists utilised an in vitro culture system of intestinal stem cells known as organoid, which resembles the 3D architecture of intestinal epithelium and faithfully recapitulates the self-renewal and differentiation processes. Researchers identified over 100 lincRNAs in intestinal stem cells and investigated their regulation by transcription factors important for stem cell maintenance and differentiation. For functional elucidation of these lincRNAs they performed gain-of-function and loss-of-function experiments in organoids using the cutting-edge CRISPR/Cas9 editing technology. Deletion of one of these lincRNAs in vivo affected intestinal stem cell viability. Although further analysis is required to unveil the precise mechanism of lincRNA function in stem cells, the current study provided unprecedented evidence on the role of lincRNAs in pluripotency and differentiation. Considering that intestinal stem cells are the origin of colon cancer, LINCRNA results may lead to the development of diagnostic markers and therapeutic targets for cancer.
Keywords
Stem cells, cancer, lincRNAs, intestinal epithelium, organoid
