The known, unknown, and unknown unknowns of cell-cell communication in planarian regeneration

Abstract

Planarians represent the most primitive bilateral triploblastic animals. Most planarian species exhibit mechanisms for whole-body regeneration, exemplified by the regeneration of their cephalic ganglion after complete excision. Given their robust whole-body regeneration capacity, planarians have been model organisms in regenerative research for more than 240 years. Advancements in research tools and techniques have progressively elucidated the mechanisms underlying planarian regeneration. Accurate cell-cell communication is recognized as a fundamental requirement for regeneration. In recent decades, mechanisms associated with such communication have been revealed at the cellular level. Notably, stem cells (neoblasts) have been identified as the source of all new cells during planarian homeostasis and regeneration. The interplay between neoblasts and somatic cells affects the identities and proportions of various tissues during homeostasis and regeneration. Here, this review outlines key discoveries regarding communication between stem cell compartments and other cell types in planarians, as well as the impact of communication on planarian regeneration. Additionally, this review discusses the challenges and potential directions of future planarian research, emphasizing the sustained impact of this field on our understanding of animal regeneration.

Extracellular vesicles promote proliferation in an animal model of regeneration

“…Identification of secreted cues that regulate proliferation after tissue injury is therefore a key goal. In planarians, only a few such cues have been identified 18,73,74 . For example, knockdown of the secreted TGF-β inhibitor Follistatin results in a dramatic reduction in stem cell proliferation with a concomitant regeneration failure 75 .…”

“…Neoblasts drive regeneration since they are the only somatic cell type capable of proliferation, and therefore the only source of new cells and tissue 17 . Although numerous extrinsic cues (e.g., axial polarity cues and extracellular matrix molecules) regulate specification and differentiation, only a few secreted factors are known to modulate neoblast proliferation 18 . Although EVs represent another potential class of extracellular regulators that could influence neoblasts, little is known about planarian EVs and/or their roles during regeneration.…”