Single-cell transcriptomics reveal ddx43+ cells as regulators of slow-cycling neoblasts in planaria

Cell cycle dynamics are fundamental to stem cell maintenance and differentiation, particularly G1-phase, yet mechanisms regulating G1 duration remain unclear. Using planaria, we uncovered how the interplay of systemic and local cues from specialized cell types regulates G1-phase progression, priming cells in slow-cycling state poised to differentiate. Single-cell transcriptomics identified G1-enriched, non-committed neoblasts that give rise to a previously uncharacterized ddx43+cell type, localized near sub-epidermal muscle and closely associated with surrounding neoblasts. Functional analyses revealed ddx43+cells maintain adjacent neoblasts in extended G1-phase and differentiation-primed state. ddx43 knockdown led to neoblast hyperproliferation, highlighting niche-like role. Following injury,Erk signalling propagates to distal regions via subepidermal muscle cells critical for suppression of ddx43+cells by downregulating Notch, establishing Erk-Notch axis cross -talk. In summary, we reveal a ddx43-dependent, non-cell autonomous mechanism regulates transient, slow-cycling neoblast population, offering new insights into how extrinsic cues orchestrate stem cell cycling during homeostasis and regeneration.