Advancing haematopoietic stem and progenitor cell biology through single-cell profiling.

Haematopoietic stem and progenitor cells (HSPCs) sit at the top of the haematopoietic hierarchy, and their fate choices need to be carefully controlled to ensure balanced production of all mature blood cell types. As cell fate decisions are made at the level of the individual cells, recent technological advances in measuring gene and protein expression in increasingly large numbers of single cells have been rapidly adopted to study both normal and pathological HSPC function. In this review we emphasise the importance of combining the correct computational models with single-cell experimental techniques, and illustrate how such integrated approaches have been used to resolve heterogeneities in populations, reconstruct lineage differentiation, identify regulatory relationships and link molecular profiling to cellular function.Research in the authors' laboratory is supported by Cancer Research UK, the Biotechnology and Biological Sciences Research Council, Bloodwise, the Leukemia and Lymphoma Society, a Wellcome Trust Strategic Award (Tracing Early Mammalian Lineage Decisions by Single Cell Genomics) and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust – MRC Cambridge Stem Cell Institute. FKH and SN gratefully acknowledge the MRC for funding of their studentships.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/1873-3468.1223