Identification of rare, transient post-mitotic cell states that are induced by injury and required for whole-body regeneration in Schmidtea mediterranea

• Published in: Nature cell biology Vol. 23; no. 9; pp. 939 - 952
• Main Authors: Benham-Pyle, Blair W., Brewster, Carolyn E., Kent, Aubrey M., Mann, Frederick G., Chen, Shiyuan, Scott, Allison R., Box, Andrew C., Sánchez Alvarado, Alejandro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2021; Nature Publishing Group
• Subjects: 14/19; 14/32; 38/77; 38/90; 631/136/142; 631/532/489; 96/100; Amputation; Analysis; Animals; Basal cells; Biomedical and Life Sciences; Cancer Research; Cell Biology; Cell differentiation; Cell division; Cell growth; Cell proliferation; Depletion; Developmental Biology; Enterocytes; Epidermal Cells - cytology; Epidermis; Follistatin; Heparan sulfate proteoglycans; Intestine; Kinases; Life Sciences; LRRK2 protein; Mediterranea - metabolism; Muscles; Pattern formation; Polarity; Progeny; Regeneration; Regeneration (Biology); Regeneration - physiology; RNA Interference - physiology; RNA-mediated interference; Schmidtea mediterranea; Stem Cells; Stem Cells - metabolism; Talin; Transcription; Transcriptome - physiology; Transcriptomes; United States
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/s41556-021-00734-6

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. Benham-Pyle et al. present a single-cell analysis of planarian regeneration and identify rare amputation-specific cell states in the muscle, epidermis and intestine that are required for patterning and stem cell proliferation.