Bone marrow hematopoietic stem cells (HSCs) are vital for the maintenance of hematopoiesis. In inbred mice housed in gnotobiotic facilities, the top of the hematopoietic hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress.
Still, whether HSC dormancy exists in human remains unclear. Our recent work shows the existence and relevance of dormancy in human HSCs and identifies the hyaluronic acid-GPRC5C signalling axis as an essential component controlling the HSC state (Zhang et al., Nature Cell Biology 2022). Further, HSCs rely on complex regulatory networks to preserve their function. Due to the scarcity of HSCs, technical challenges have limited our insights into the interplay between HSC metabolism and their transcriptional and epigenetic regulation.
We recently established and integrated low-input multi-layer OMICs data revealing distinct metabolic and epigenetic hubs that are enriched in HSCs and their downstream multipotent progenitors (Schönberger et al., Cell Stem Cell 2022). Mechanistically, we uncover a non-classical retinoic acid signaling axis that regulates HSC identity. Our findings emphasize how a single metabolite controls stem cell fate by instructing epigenetic and transcriptional attributes. Now we have translated these finding in the context of myocardial infract.