Dynamic cell fate transitions during morphallactic regeneration

Regeneration can proceed through epimorphosis, involving regrowth of lost structures at the amputation site in a proximal-to-distal sequence, or through morphallaxis, which is characterized by extensive tissue remodeling with minimal cell proliferation. While the mechanisms underlying epimorphic regeneration are well studied, the spatiotemporal dynamics of morphallaxis remain less understood. Here we show, using time-course single-cell RNA sequencing (scRNA-seq) of regenerating Hydra tissue, that morphallaxis involves a temporal sequence in the re-emergence of terminal and subterminal cell identities, with transcriptional signatures associated with proximal structures appearing earlier than those of distal structures. We further find that Wnt signaling remains dynamically active at the amputation site throughout regeneration, with its composition changing over time, consistent with a transient regulatory state. Together, these findings provide a high-resolution view of dynamic cell state transitions and signaling activity during morphallactic regeneration and offer a framework for exploring how organizer function and axial patterning are re-established in Hydra. This study maps how cells change identity over time during Hydra regeneration, revealing that positional information and Wnt signaling evolve dynamically to guide the stepwise re-establishment of the body axis.