RT Journal Article SR Electronic T1 Identification of rare transient somatic cell states induced by injury and required for whole-body regeneration JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.04.132753 DO 10.1101/2020.06.04.132753 A1 Benham-Pyle, Blair W. A1 Brewster, Carolyn E. A1 Kent, Aubrey M. A1 Mann, Frederick G. A1 Chen, Shiyuan A1 Scott, Allison R. A1 Box, Andrew C. A1 Alvarado, Alejandro Sánchez YR 2020 UL http://biorxiv.org/content/early/2020/06/06/2020.06.04.132753.abstract AB Regeneration requires functional coordination of stem cells, their progeny, and differentiated cells. Past studies have focused on regulation of stem cell identity and proliferation near to the wound-site, but less is known about contributions made by differentiated cells distant to the injury. Here, we present a comprehensive atlas of whole-body regeneration over time and identify rare, transient, somatic cell states induced by injury and required for regeneration. To characterize amputation-specific signaling across a whole animal, 299,998 single-cell transcriptomes were captured from planarian tissue fragments competent and incompetent to regenerate. Amputation-specific cell states were rare, non-uniformly distributed across tissues, and particularly enriched in muscle (mesoderm), epidermis (ectoderm), and intestine (endoderm). Moreover, RNAi-mediated knockdown of genes up-regulated in amputation-specific cell states drastically reduced regenerative capacity. These results identify novel cell states and molecules required for whole-body regeneration and indicate that regenerative capacity requires transcriptional plasticity in a rare subset of differentiated cells.Competing Interest StatementThe authors have declared no competing interest.