RT Journal Article
SR Electronic
T1 Assessment of clonal kinetics reveals multiple trajectories of dendritic cell development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 167635
DO 10.1101/167635
A1 Dawn Lin
A1 Andrey Kan
A1 Jerry Gao
A1 Edmund Crampin
A1 Philip D. Hodgkin
A1 Shalin H. Naik
YR 2017
UL http://biorxiv.org/content/early/2017/08/12/167635.abstract
AB 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) from barcode-labeled hematopoietic stem and progenitor cells (HSPCs) by serially measuring barcode signatures, and visualize this multidimensional data using novel developmental interpolated t-distributed stochastic neighborhood embedding (Di-SNE) 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.