Developmental Paths

Do Intermediate Progenitors function as critical conduits on the path(s) to differentiation? In other words, does the developmental path a cell takes influence its fate?

Years of mammalian hematopoiesis research have produced a basic roadmap, delineating a series of critical decision points that collectively define a "path" or "route" guiding the cell's transition from an immature to a mature state. These decision-point intersections are often characterized by transient intermediate progenitor (IP) cells, which are thought to act as “transit amplifying” populations but serve no distinct biological role. Our data suggests that multiple IP paths exist and play different biological roles during blood cell development. Contrary to the prevailing paradigm that activation of specific signaling pathways is sufficient to control cell fat, our findings suggest that flux through alternative cellular pathways influences the balance between progenitor maintenance and differentiation, and may affect the functional output of mature blood cells derived from one path versus another. Our studies will provide a molecular framework for understanding how subtype specificity is established, and a new paradigm for studying how developmental paths affect mature cellular functions.