摘要：SummaryHigh-dimensional single cell profiling coupled with computational modeling is emerging as a powerful tool to elucidate developmental programs directing cell lineages. We introduce tSpace, an algorithm based on the concept of “trajectory space”, in which cells are defined by their distance along nearest neighbor pathways to every other cell in a population. Graphical mapping of cells in trajectory space allows unsupervised reconstruction and exploration of complex developmental sequences. Applied to flow and mass cytometry data, the method faithfully reconstructs thymic T cell development and reveals development and trafficking regulation of tonsillar B cells. Applied to the single cell transcriptome of mouse intestine andC. elegans, the method recapitulates development from intestinal stem cells to specialized epithelial phenotypes more faithfully than existing algorithms and ordersC. eleganscells concordantly to the associated embryonic time. tSpace profiling of complex populations is well suited for hypothesis generation in developing cell systems.Graphical AbstractDisplay OmittedHighlights•tSpace: trajectory analysis agnostic to biological systems and technology platforms•tSpace faithfully reconstructs complex developmental trees within one or more tissues•tSpace reveals rare transient cells usually missed by trajectory inference algorithms•tSpace confirms known and unveils novel biology in human B cells and mouse intestineDevelopmental Biology; Systems Biology; In Silico Biology
