Regeneration requires the coordination of stem cells, their progeny and distant differentiated tissues. Here, we present a comprehensive atlas of whole-body regeneration in Schmidtea mediterranea and identify wound-induced cell states. An analysis of 299,998 single-cell transcriptomes captured from regeneration-competent and regeneration-incompetent fragments identified transient regeneration-activated cell states (TRACS) in the muscle, epidermis and intestine. TRACS were independent of stem cell division with distinct spatiotemporal distributions, and RNAi depletion of TRACS-enriched genes produced regeneration defects. Muscle expression of notum, follistatin, evi/wls, glypican-1 and junctophilin-1 was required for tissue polarity. Epidermal expression of agat-1/2/3, cyp3142a1, zfhx3 and atp1a1 was important for stem cell proliferation. Finally, expression of spectrinβ and atp12a in intestinal basal cells, and lrrk2, cathepsinB, myosin1e, polybromo-1 and talin-1 in intestinal enterocytes regulated stem cell proliferation and tissue remodelling, respectively. Our results identify cell types and molecules that are important for regeneration, indicating that regenerative ability can emerge from coordinated transcriptional plasticity across all three germ layers.

再生需要干细胞、其后代和远处分化组织的协调。在这里，我们展示了地中海 Schmidtea全身再生的综合图谱，并确定了伤口诱导的细胞状态。对从有再生能力和无再生能力片段中捕获的 299,998 个单细胞转录组进行分析，确定了肌肉、表皮和肠道中的瞬时再生激活细胞状态 (TRACS)。 TRACS 独立于干细胞分裂，具有不同的时空分布，并且 TRACS 富集基因的 RNAi 耗竭会产生再生缺陷。组织极性需要notum 、卵泡抑素、 evi/wls 、磷脂酰肌醇蛋白聚糖-1和junctophilin-1的肌肉表达。 agat-1 / 2 / 3 、 cyp3142a1 、 zfhx3和atp1a1的表皮表达对于干细胞增殖很重要。最后，肠基底细胞中血影蛋白β和atp12a的表达，以及肠肠上皮细胞中lrrk2 、组织蛋白酶B 、肌球蛋白1e 、 polybromo-1和talin-1的表达分别调节干细胞增殖和组织重塑。我们的结果确定了对再生重要的细胞类型和分子，表明再生能力可以从所有三个胚层的协调转录可塑性中产生。