Mapping high-resolution cell phylogenies reveals age-dependent loss of lineage diversity in the Drosophila midgut

Age-related changes in stem cell pool maintenance and proliferative behavior play a critical role in the aging of multicellular tissues. In this study, we investigated these changes in the adult Drosophila midgut using SMALT, a modified lineage tracing system. By constructing cell phylogenetic trees across different age groups, we observed a significant age-dependent decline in both effective population size and lineage diversity within the midgut cell population. To specifically track intestinal stem cells (ISCs), we developed a Dl-GAL4-driven SMALT system, revealing a pronounced reduction in ISC lineage diversity in aged fruit flies. Notably, lineages that initiated expansion during youth exhibited a competitive growth advantage over those that expanded later in old age. These findings offer valuable insights into the age-dependent dynamics of stem cell populations and their implications for tissue maintenance during aging.