An unexpected mode of whole-body regeneration from reaggregated cell suspension in Hydractinia (Cnidaria, Hydrozoa)

Hydrozoan cnidarians are among the few animals that can regenerate whole bodies from reaggregated cell dissociations but the cellular and molecular mechanisms that control this ability and how it is related to embryonic development are not well understood. Furthermore, the evolution of this type of regeneration is enigmatic since it does not occur naturally. Here, we show that aggregate regeneration in Hydractinia symbiolongicarpus proceeds through several, consistent stages that include the formation of an epidermal layer, followed by migration, proliferation, and differentiation of adult pluripotent stem cells, known as i-cells. Migration of i-cells is controlled by sphingosine-1-phosphate signaling. Single-cell transcriptomics revealed, surprisingly, that the newly regenerated individual derives nearly exclusively from i-cell progeny rather than from recycled somatic cells, as seen in other hydrozoans. Given the similarity of this phenomenon to embryogenesis, we propose that the ability of Hydractinia cell aggregates to regenerate is a side effect of the animal’s i-cell-mediated development.