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New Insights into Haematopoietic Differentiation Landscapes from scRNA-seq

Sam Watcham, Iwo Kucinski and Berthold Gottgens

Abstract

Single cell transcriptomics has recently emerged as a powerful tool to analyse cellular heterogeneity, discover new cell types and infer putative differentiation routes. The technique has been rapidly embraced by the haematopoiesis research community and like other technologies before, single cell molecular profiling is widely expected to make important contributions to our understanding of the haematopoietic hierarchy. Much of this new interpretation relies on inference of the ‘transcriptomic landscape’ as a representation of existing cellular states and associated transitions between them. Here we review how this model allows, under certain assumptions, charting of ‘time-resolved’ differentiation trajectories with unparalleled resolution and how the landscape of multipotent cells may be rather devoid of discrete structures, challenging our preconceptions about stem and progenitor cell types and their organisation. Finally, we highlight how promising technological advances may convert static differentiation landscapes into a dynamic cell flux model and thus provide a more holistic understanding of normal haematopoiesis and blood disorders.

  • Submitted August 15, 2018.
  • Accepted October 22, 2018.