Fibrillarin-1 and Fibrillarin-2 are required for divergent cell lineage development in planarian homeostasis and regeneration

Ribosome heterogeneity has been revealed to exist in different cell types during development. However, the function and regulatory mechanisms of ribosome heterogeneity in missing tissue regeneration have yet to be reported. We used the planarian Schmidtea mediterranea with whole-body regenerative capability as a model and revealed the function of the rRNA modification protein fibrillarin in cell lineage development and tissue regeneration. We identified two fibrillarin homologs in planarian, Smed-fbl-1 ( fbl-1 ) and Smed-fbl-2 ( fbl-2 ), with distinct expression patterns. While fbl-2 regulates stem cell proliferation and multiple progenitor cell differentiation, fbl-1 participates in epidermal lineage late-stage specification and wound response. This study indicates that fibrillarin, a nucleolar protein, can respond to wounds and function in distinct cell types, suggesting the existence and critical roles of ribosome heterogeneity in stem cells and tissue regeneration. ### Competing Interest Statement The authors have declared no competing interest.