1. Polycomb group genes (PcG) as key self-renewal determinants
Hox and Polycomb Group (PcG) genes are key regulators of HSC self-renewal. PcG proteins form 2 distinct complexes: BMI1-RING1 (PRC1) and EZH1/2 (PRC2).
Our lab has shown that PRC1 exert pro-proliferative, and
PRC2 anti-proliferative effects on HSCs1-2.
Through interactions with numerous co-factors identified in our laboratory such
as E4F13, UBAP2L4 and MAP1S, we found that BMI1 exerts several non-canonical functions to regulate HSC activity. Most intriguingly, we recently identified a BMI1-E4F1-CHK1 interaction complex that appears to control centrosome numbers and cell cycle checkpoints in HSCs
We now aim to decipher the role of PcG genes to HSC self-renewal, by focusing on the non-chromatin functions of this complex. We will also continue to study the molecular basis underlying the opposing function of PRC1 and PRC2 in HSC activity using
CRISPR, shRNA, gene targeting and gain of function approaches.