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

Dawn S Lin; Andrey Kan; Jerry Gao; Edmund J Crampin; Philip D Hodgkin; Shalin H Naik

doi:10.1016/j.celrep.2018.02.046

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

Cell Rep. 2018 Mar 6;22(10):2557-2566. doi: 10.1016/j.celrep.2018.02.046.

Authors

Dawn S Lin¹, Andrey Kan², Jerry Gao³, Edmund J Crampin⁴, Philip D Hodgkin², Shalin H Naik⁵

Affiliations

¹ Molecular Medicine Division, Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; Immunology Division, Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
² Immunology Division, Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
³ Molecular Medicine Division, Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia.
⁴ Systems Biology Laboratory, University of Melbourne, Parkville, VIC 3010, Australia; Centre for Systems Genomics, University of Melbourne, Parkville, VIC 3010, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Melbourne School of Engineering, University of Melbourne, Parkville, VIC 3010, Australia.
⁵ Molecular Medicine Division, Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; Immunology Division, Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: naik.s@wehi.edu.au.

PMID: 29514085
DOI: 10.1016/j.celrep.2018.02.046

Abstract

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.

Keywords: DiSNE; cellular barcoding; cellular trajectory; dendritic cells; fate; hematopoiesis; kinetics; lineage; single cell; t-SNE.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Clone Cells
Dendritic Cells / cytology*
Kinetics
Male
Mice, Inbred C57BL
Stochastic Processes
Time-Lapse Imaging*