Mechanisms of Development and Regeneration in Hydra

The adult Hydra continually renews all cells using lineage-restricted adult stem cells and can regenerate its entire body from a small piece of tissue. The goal of our research is to: 1) understand the signaling pathways and gene regulatory networks that underlie homeostatic maintenance and 2) understand how these homeostatic mechanisms are activated at ectopic locations to rebuild structures during regeneration. Both homeostatic maintenance and regeneration requires the coordination of three non-overlapping stem cell differentiation pathways. This complexity of cell fate specification pathways is combined with a simple tissue structure and a small number of total cell types. This unique combination of traits in Hydra allowed us to use single cell RNA sequencing to capture the spectrum of cell states in a homeostatic animal at high molecular resolution and use this information to decipher the stem cell differentiation pathways of multiple distinct lineages. We sequenced the transcriptomes of ~25,000 Hydra cells and identified the molecular signatures of cell states, from stem cells to terminally differentiated cells. We constructed differentiation trajectories for each lineage and identified the transcription factors expressed along these trajectories, thus creating a multi-lineage map of an adult organism that provides insights into the regulatory mechanisms underlying cell renewal in a homeostatic animal. To understand how these pathways are transcriptionally activated in response to major injury, we collected RNA-seq and ATAC-seq data at early regeneration time points. These data suggest that transcription factors associated with the conserved injury response activate the transcription of Wnt ligands. We hypothesize that this triggers the formation of a new organizer at the site of injury that directs formation of regenerating structures.