4. Temporospatial control of cell fate reprogramming
Natural lineage reprogramming, the conversion of one cell identity to another during normal development, although rare, occurs with high efficiency and temporospatial precision. These natural lineage conversion events provide powerful model systems for deciphering the mystery of cellular plasticity. We recently uncovered a natural midgut-to-renal lineage reprogramming event during fruit fly metamorphosis and identified a highly conserved protein called Cut as a crucial cell identity switch in this process. A steep gradient of a spatial molecule (called Wingless/Wg) intersects with a pulse of steroid hormone to induce Cut expression specifically in a small subset of fly midgut progenitors, precursors that produce functional midgut cells, and convert them into renal identity. Intriguingly, the temporal and spatial signals triggering this natural lineage reprogramming event likely intersect through an unexpected chromatin looping mechanism. The mechanism we unveiled here might represent a new and general paradigm governing cell fate or identity switch with high precision in space and time, and has promising implications for the development of regenerative medicine strategies. (Xu K, et al., 2018b, eLife).