DiSNE Movie Visualization and Assessment of Clonal Kinetics Reveal Multiple Trajectories of Dendritic Cell Development

Summary: A thorough understanding of cellular development is incumbent on assessing the complexities of fate and kinetics of individual clones within a population. Here, we develop a system for robust periodical assessment of lineage outputs of thousands of transient clones and establishment of bona fide cellular trajectories. We appraise the development of dendritic cells (DCs) in fms-like tyrosine kinase 3 ligand culture from barcode-labeled hematopoietic stem and progenitor cells (HSPCs) by serially measuring barcode signatures and visualize these multidimensional data using developmental interpolated t-distributed stochastic neighborhood embedding (DiSNE) time-lapse movies. We identify multiple cellular trajectories of DC development that are characterized by distinct fate bias and expansion kinetics and determine that these are intrinsically programmed. We demonstrate that conventional DC and plasmacytoid DC trajectories are largely separated already at the HSPC stage. This framework allows systematic evaluation of clonal dynamics and can be applied to other steady-state or perturbed developmental systems. : Lin et al. develop a framework to longitudinally track and visualize clonal cellular trajectories during dendritic cell development. The authors demonstrate that properties including fate bias and the timing and size of clonal bursts are heterogeneous within populations yet largely imprinted in single progenitors at early developmental stages. Keywords: dendritic cells, hematopoiesis, single cell, cellular barcoding, t-SNE, DiSNE, lineage, fate, kinetics, cellular trajector