Highlights d Unbiased atlas of cell types throughout mouse digit tip regeneration d The early blastema contains all broad cell lineages found in the unamputated digit tip d Fibroblasts are the most abundant and heterogeneous population d Dynamics of distinct fibroblast populations reveal regeneration-specific markers
14Innate regeneration following digit tip amputation is one of the few examples of epimorphic 15 regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure 16 invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses in 17 mice, the digit tip blastema has been defined as a population of heterogeneous, lineage restricted 18 progenitor cells. These previous studies, however, do not comprehensively evaluate blastema 19 heterogeneity or address lineage restriction of closely related cell types. In this report we present 20 single cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and 21 unamputated control digit tips and generate an atlas of the cell types participating in digit tip 22 regeneration. We define the differentiation trajectories of vascular, monocytic, and fibroblastic 23 lineages over regeneration, and while our data confirm broad lineage restriction of progenitors, 24 our analysis reveals an early blastema fibroblast population expressing a novel regeneration-25
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