Space-Time Mapping Identifies Concerted Multicellular Patterns and Gene Programs in Healing Wounds and their Conservation in Cancers

Abstract

Tissue repair responses in metazoans are highly coordinated by different cell types over space and time. However, comprehensive single-cell based characterization covering this coordination is lacking. Here, we captured transcriptional states of single cells over space and time during skin wound closure, revealing choreographed gene expression profiles. We identified shared and prominent space-time patterns of cellular and gene expression enrichment: which we call multicellular movements and which spanned multiple cell types. We validated some of the discovered space-time movements using large volume imaging of cleared wounds and demonstrated the value of this analysis to predict gene products made by macrophages or fibroblasts, which activated gene programs in the opposite cell type. Finally, using two different tumor models, we tested the hypothesis that tumors are like wounds that never heal finding conserved wound healing movements in the tumor space, wherein some movements were preferentially used in one tumor versus another. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/493500v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@12a03e3org.highwire.dtl.DTLVardef@1654966org.highwire.dtl.DTLVardef@b603c0org.highwire.dtl.DTLVardef@1b05998_HPS_FORMAT_FIGEXP M_FIG C_FIG