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、它们的后代和远距离分化组织的协调。在这里，我们提出了一个全面的Schmidtea mediterranea全身再生图谱，并确定了伤口诱导的细胞状态。对从具有再生能力和不能再生能力的片段中捕获的 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 不依赖于具有不同时空分布的干细胞分裂，并且富含 TRACS 的基因的 RNAi 消耗会产生再生缺陷。notum 、follistatin、evi/wls 、 glypican -1和junctophilin-1是组织极性所必需的。agat-1 / 2 / 3、cyp3142a1、zfhx3和atp1a1的表皮表达对干细胞增殖很重要。最后， Spectrinβ和atp12a在肠基底细胞中的表达，以及lrrk2、组织蛋白酶B 、肌球蛋白1e、polybromo -1和talin-1在肠上皮细胞中，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很重要的细胞类型和分子，表明再生能力可以来自所有三个胚层的协调转录可塑性。