A generic and cell-type-specific wound response precedes regeneration in planaria

Omri Wurtzel^1,2, Lauren Cote^1,2, Amber Poirier^1,2, Rahul Satija^3,4, Aviv Regev^2,3, and Peter W. Reddien^1,2,*
Wurtzel et al. Developmental Cell , Volume 35 , Issue 5 , 632 - 645

Regeneration starts with injury. Yet how injuries affect gene expression in different cell types and how distinct injuries differ in gene expression remain unclear. We defined the transcriptomes of major cell types of planarians—flatworms that regenerate from nearly any injury—and identified 1,214 tissue-specific markers across 13 cell types. RNA sequencing on 619 single cells revealed that wound-induced genes were expressed either in nearly all cell types or specifically in one of three cell types (stem cells, muscle, or epidermis). Time course experiments following different injuries indicated that a generic wound response is activated with any injury regardless of the regenerative outcome. Only one gene, notum, was differentially expressed early between anterior- and posterior-facing wounds. Injury-specific transcriptional responses emerged 30 hr after injury, involving context-dependent patterning and stem-cell-specialization genes. The regenerative requirement of every injury is different; however, our work demonstrates that all injuries start with a common transcriptional response.

t-SNE embedding of single cells based on gene expression. Each cell is represented by a dot colored according to density clustering assignment. The Cluster label was determined by detection of multiple, known, cell-specific markers, or by ISH experiments. Cells shown are from the 2C fraction (wounded and unwounded) and 4C (unwounded).

1. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
2. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
4. New York Genome Center, New York, New York, USA and Department of Biology, New York University, New York, New York, USA.
5. Correspondence: reddien@wi.mit.edu

The planaria single-cell page is hosted by the Reddien lab @ The Whitehead Institute