Synergistic rewiring of transcriptional networks in accordance with environmental and metabolic signals is necessary to ensure the successful progression of early mammalian development. Epigenetic regulation is central to cellular identity, as functional diversification is achieved through interpretation of the same DNA that all cells of the organism share. Incomplete or altered epigenetic landscapes can lead to developmental and long-term disorders. Despite the central role of metabolism in development and disease, how metabolic pathways regulate epigenetic landscapes during early embryonic development remains elusive.
Pluripotent cells arise in the preimplantation embryo, can be propagated indefinitely in vitro as embryonic stem (ES) cells, and have been under the spotlight for decades due to their ability to give rise to all cell types of the body. Pluripotency is paradoxically a transient state in vivo, lasting 2-3 days in mice around the time of blastocyst implantation. The timing of emergence and dissolution of pluripotency is essential to the successful progression of mammalian development. Interestingly, an abnormal reversion to an undifferentiated state later in life is often associated with disease phenotypes.
Our lab aims to dissect the crosstalk between metabolism and chromatin in pluripotent stem cells. Our research strategy integrates in vivo and in vitro techniques, biochemistry, imaging, molecular and developmental biology to study the above questions. Metabolo-epigenetic regulation is widely relevant to numerous cell types across organisms, particularly to stem/progenitor populations at the forefront of quiescence vs proliferation decisions in embryonic and adult tissues and disease states. We aim to integrate other stem cell models such as neural stem/progenitor cells in our research to uncover regulatory pathways critical for the timing of proliferation across mammalian stem cells.