New insights into hematopoietic differentiation landscapes from single-cell RNA sequencing.


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Article
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Abstract

Single-cell transcriptomics has recently emerged as a powerful tool to analyze cellular heterogeneity, discover new cell types, and infer putative differentiation routes. The technique has been rapidly embraced by the hematopoiesis research community, and like other technologies before, single-cell molecular profiling is widely expected to make important contributions to our understanding of the hematopoietic hierarchy. Much of this new interpretation relies on inference of the transcriptomic landscape as a representation of existing cellular states and associated transitions among 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 organization. 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 hematopoiesis and blood disorders.

Publication Date
2019-03-28
Online Publication Date
2019-02-06
Acceptance Date
2018-10-22
Keywords
Animals, Hematopoiesis, Hematopoietic Stem Cells, Humans, Sequence Analysis, RNA, Single-Cell Analysis
Journal Title
Blood
Journal ISSN
0006-4971
1528-0020
Volume Title
133
Publisher
American Society of Hematology
Sponsorship
Wellcome Trust (105031/D/14/Z)
Cancer Research UK (21762)
Medical Research Council (MR/M008975/1)
National Institute of Diabetes and Digestive and Kidney Diseases (R24DK106766)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/S036113/1)
Work in the Gottgens Laboratory is funded by grants from Wellcome; Bloodwise; Cancer Research UK; National Institutes of Health (NIDDK DK106766); and core support grants by Wellcome to the Wellcome–Medical Research Council Cambridge Stem Cell Institute. SW is the recipient of a Medical Research Council Studentship.