Epigenetic regulation of HSCs

Epigenetic regulation, including non-coding RNAs, DNA methylation, histone modification, and chromatin remodeling, has been shown to play essential roles in regulating HSCs and orchestrating the balance between HSC maintenance and action. We initiated our study on epigenetic regulation of HSCs by seeing a differential expression of imprinted genes in HSCs (Haug and He et al., Cell Stem Cell, 2008). Further, we functionally proved that the imprinting at the H19-Igf2 locus is essential for maintaining HSC quiescence via suppression of Igf1r expression by H19-derived miR-675 (Venkatraman et al., Nature, 2013). Recently, we identified the critical role of the imprinted Dlk1-Gtl2 locus in preserving the functionality of the most primitive HSCs by inhibiting mitochondrial biogenesis and metabolism through suppressing the entire mTOR pathway (Qian et al., Cell Stem Cell, 2016). Currently, we are systematically investigating the long non-coding RNAs profiling, as well as status of DNA methylation and histone modification in HSCs, committed progenitors and mature effect cells.