Hydra, a simple aquatic animal, undergoes continual self-renewal, lacks senescence, and has robust regenerative capabilities; this is accomplished using the same basic molecular toolkit that vertebrates possess. The aim of our research is to understand the molecular mechanisms that underlie these processes in Hydra (Figure 1).
Using single cell RNA sequencing to uncover differentiation trajectories in Hydra
Single cell RNA sequencing (scRNA-seq) technology is rapidly advancing the field of developmental biology. Collecting thousands of single cell transcriptomes over a developmental time course allows for the ordering of cells into differentiation trajectories by taking advantage of progressive changes in gene expression. This strategy reveals the complete set of genes that underlie cell fate decisions, including rare cell states at key decision branch points, thus giving researchers an unprecedented view of development. We are applying this approach to the adult Hydra, which continually replaces all cells every 20 days through a combination of stem cell differentiation and transdifferentiation events. Therefore, by performing scRNA-seq on one time point (the steady-state adult Hydra), we are able to uncover all differentiation pathways. Using this strategy we are building a molecular map of Hydra homeostatic development.
Understanding how injury triggers developmental pathways during regeneration
In regenerative animals, injury reactivates developmental processes in the adult, in part through the action of conserved injury-response transcription factors. These conserved transcription factors are upregulated in response to injury even in non-regenerative wounds. Thus an important questions is: why do the same transcription factors trigger development in some tissue contexts or animals, but not others? We aim to shed light on this question by uncovering gene regulatory links in Hydra between injury-induced transcription factors and developmental gene regulatory networks active in the adult.
The PIWI-piRNA pathway and the maintenance genomic integrity in Hydra stem cells
The PIWI-piRNA pathway is a small RNA pathway best known for protecting the germline from transposable element (TE) mobilization, which would otherwise lead to genomic toxicity and deleterious mutations. At the center of the pathway are PIWI proteins, which are bound to small RNAs called PIWI-interacting RNAs or piRNAs (~24-31 nucleotides). Cytoplasmic PIWI proteins have a conserved function in post-transcriptionally repressing transposons in animals germlines. In addition there are an increasing number of documented cases of piwi expression in somatic tissues. We find that the PIWI-piRNA pathway has a critical function in the somatic stem cells of Hydra, which is a long-lived freshwater cnidarian. It has been hypothesized that the function of the PIWI-piRNA pathway in the somatic cells of long-lived animals contributes to longevity through the repression of TEs. In our current research, we are testing this hypothesis by identifying RNA targets of the pathway in Hydra somatic cells.