Regeneration is a concerted effort involving multiple stem cells. While individual stem cells may be differentially regulated, their overall activities must be strictly coordinated to ensure proper tissue size and function. Cellular heterogeneity and defects in cellular coordination are major hurdles in treating many diseases including cancer.
Our research is driven by three major areas of interest: (1) How are individual HSCs regulated to produce different amounts and types of blood cells? How can we exploit the mechanisms underlying the cellular differences to control the overall stem cell population and to improve bone marrow transplantation? (2) How are distinct HSCs coordinated to ensure an overall balanced blood supply? And how does miscommunication between stem cells cause diseases? (3) How do individual cell clones differentially contribute to cancer genesis, metastasis and relapse? And how to design therapeutic treatments that target the responsible clones?
HSCs play a pivotal role in bone marrow transplantation, the earliest and by far the most prevalent stem cell therapy. Our recent studies show that HSC differentiation is substantially altered by the conditioning regimen used during the transplantation. (See figure.) If a recipient is treated with conditioning such as irradiation prior to transplantation, individual HSCs produce distinct numbers of blood cells and differentially supply different cell types. This HSC coordination pattern persists throughout the recipient’s lifetime. In contrast, in the absence of pre-transplantation conditioning, individual HSCs uniformly supply the blood. We have also found that changes to HSC coordination are not random or stochastic, but instead are rigorously regulated at distinct steps of HSC differentiation. These findings are undetectable at the population level and provide a new framework for understanding stem cell regulation and tissue regeneration at the single cell level.