Stem cells partner with matrix remodeling cells during regeneration

Regeneration of missing or damaged tissue requires the concerted activities of both pre-existing and newly generated cells. While previous studies identified regeneration-induced gene expression programs in tissues and single cells, emerging spatial transcriptomic methods can place these programs into their organismal context at near cellular resolution. Here we report a spatial transcriptomic atlas of whole-body regeneration and identify changes in gene expression patterning and tissue architecture during regeneration. We produced spatially resolved RNA-seq data from regenerating tail fragments of the free-living planarian Schmidtea mediterranea. Comparison of fragments 6 and 48 hours after amputation revealed time-dependent changes in gene expression patterns and cellular associations. Notable examples include re-localization of agat-1⁺ epidermal cells from lateral edges to both lateral and anterior edges and the discovery of wound-induced association of stem cells with cells expressing the matrix remodeling gene matrix metalloproteinase-1. Our results thoroughly detail changes in gene expression patterns and uncover interactions between stem cells and their microenvironment, demonstrating the unique ability of unbiased spatial profiling methods to reveal the biology of regeneration.