Small RNA Regulation of Stem Cell Self-Renewal and Differentiation
The molecular controls that govern stem cell differentiation remain poorly understood. A major goal of our laboratory's research is to identify global regulators involved in establishing and maintaining the differentiated cell fate. In particular, we are interested in those mechanisms that silence previously active stem cell programs upon differentiation. Epigenetics play a critical role in this process. Well-established epigenetic silencers include DNA methylation and histone modifications. However, there is also emerging evidence for new class of epigenetic silencers, non-coding small RNAs. Non-coding small RNAs are predicted to regulate large regions of genome and proteome, making them excellent candidates to direct and maintain the large shifts in a cell's constitution associated with differentiation. Non-coding small RNAs can be further subdivided into different classes that differ in their biogenesis and mechanism of action. These classes include microRNAs (miRNAs), small interfering RNAs (siRNAs), and piwi-interacting RNAs (piRNAs). Our laboratory is working to systematically study the role of these various classes of small RNAs in embryonic and somatic stem cell differentiation. In addition, we are interested in how the small RNAs interact with the other global epigenetic regulators of differentiation including DNA methylation and histone modifications. Our work should provide new paradigms for the molecular control of cellular differentiation with important implications for normal development and disease.