Regulation of cellular plasticity and regeneration in Drosophila spermatogenesis

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

Abstract Adult tissues typically rely on self-renewing stem cells to sustain tissue homeostasis. In response to injury, however, additional cells can be recruited to participate in regeneration, or the regrowth of lost tissues or organs. Understanding regeneration is a longstanding goal in biology. Cells that can adopt the biological properties of other cell types under specific conditions, or possess cellular plasticity, are key contributors to regeneration, but their regulation is poorly understood. By developing the Drosophila testis as a model system to study the biology of stem cells and their microenvironments, or niches, we have discovered unexpected cellular plasticity among the constituent cell types. Advantages of this system include the relative simplicity of the tissue and an unparalleled collection of genetic tools with which to probe it functionally. Our ability to genetically manipulate cells in vivo and then determine the effects on stem cell function has led to several foundational discoveries. Previously, we showed that damaging the Drosophila testis causes differentiating germ cells to dedifferentiate, becoming new germline stem cells that can repair the tissue. We also found that quiescent somatic niche cells can transdifferentiate into new somatic stem cells upon tissue damage. Here we combine live imaging, lineage tracing, and results from our recent single cell transcriptomic profiling of this tissue to determine how niches sense damage and then activate program(s) to regenerate missing stem cells. We also characterize candidate signals that relay information from stem cells back to their niche. Finally, we investigate the role of newly identified genes that could function in organism-wide communication with the niche. Our synergistic approach will enhance the understanding of the fundamental cellular and molecular mechanisms regulating stem cell renewal in the testis, which has important implications for understanding male fertility and regeneration.