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Emerging single-cell tools are primed to reveal functional and molecular heterogeneity in malignant hematopoietic stem cells

Shepherd, Mairi S.a,b; Kent, David G.a,b

Current Opinion in Hematology: July 2019 - Volume 26 - Issue 4 - p 214–221
doi: 10.1097/MOH.0000000000000512
HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano

Purpose of review The recent emergence of single-cell technologies has permitted unprecedented insight into the molecular drivers of fate choice in blood stem and progenitor cells. This review gives a broad overview of current efforts to understand the molecular regulators of malignant hematopoietic stem cells (HSCs) at the single-cell level.

Recent findings The large-scale adoption of single-cell approaches has allowed extensive description of the transcriptional profiles and functional properties of single HSCs. These techniques are now beginning to be applied to malignant HSCs isolated directly from patients or from mouse models of malignancy. However, these studies have generally struggled to pinpoint the functional regulators of malignant characteristics, since malignant HSCs often differ in more than one property when compared with normal HSCs. Moreover, both normal and malignant populations are complicated by HSC heterogeneity.

Summary Despite the existence of single-cell gene expression profiling tools, relatively few publications have emerged. Here, we review these studies from recent years with a specific focus on those undertaking single-cell measurements in malignant stem and progenitor cells. We anticipate this to be the tip of the iceberg, expecting the next 2–3 years to produce datasets that will facilitate a much broader understanding of malignant HSCs.

aWellcome-MRC Cambridge Stem Cell Institute

bDepartment of Haematology, University of Cambridge, Cambridge, UK

Correspondence to David G. Kent, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, UK. Tel: +44 1223 762130; e-mail:

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