Molecular profiles, sources and lineage restrictions of stem cells in an annelid regeneration model

• Published in: Nature communications 2024-11, Vol.15 (1), p.9882-18, Article 9882
• Main Authors: Stockinger, Alexander W., Adelmann, Leonie, Fahrenberger, Martin, Ruta, Christine, Özpolat, B. Duygu, Milivojev, Nadja, Balavoine, Guillaume, Raible, Florian
• Format: Article
• Language: English
• Subjects: 14/19; 38/32; 38/91; 42/109; 631/136/532/2063; 631/136/532/489; 631/532/2118; 96/95; Amputation; Animal biology; Animal models; Animals; Biochemistry, Molecular Biology; Body parts; Cell culture; Cell Lineage; Cell Lineage - genetics; Constrictions; Development Biology; Epidermis; Gene expression; Gene sequencing; Genomics; Humanities and Social Sciences; Invertebrate Zoology; Life Sciences; Molecular modelling; multidisciplinary; Polychaeta; Polychaeta - genetics; Regeneration; Regeneration - genetics; Science; Science (multidisciplinary); Single-Cell Analysis; Stem Cells; Stem Cells - cytology; Stem Cells - metabolism; Vertebrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-54041-3

Regeneration of missing body parts can be observed in diverse animal phyla, but it remains unclear to which extent these capacities rely on shared or divergent principles. Research into this question requires detailed knowledge about the involved molecular and cellular principles in suitable reference models. By combining single-cell RNA sequencing and mosaic transgenesis in the marine annelid Platynereis dumerilii , we map cellular profiles and lineage restrictions during posterior regeneration. Our data reveal cell-type specific injury responses, re-expression of positional identity factors, and the re-emergence of stem cell signatures in multiple cell populations. Epidermis and mesodermal coelomic tissue produce distinct putative posterior stem cells (PSCs) in the emerging blastema. A novel mosaic transgenesis strategy reveals both developmental compartments and lineage restrictions during regenerative growth. Our work supports the notion that posterior regeneration involves dedifferentiation, and reveals molecular and mechanistic parallels between annelid and vertebrate regeneration. Regenerative capacity varies between species, with some animals showing robust whole-animal regeneration after amputation. Here they use time-resolved scRNA-seq and mosaic transgenesis to delineate how stem cells re-emerge after amputation in an annelid worm, and reveal unexpected parallels to vertebrate regeneration models.