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Review
. 2018 Mar 1;2(2):e34.
doi: 10.1097/HS9.0000000000000034. eCollection 2018 Mar-Apr.

Single-Cell Sequencing in Normal and Malignant Hematopoiesis

Affiliations
Review

Single-Cell Sequencing in Normal and Malignant Hematopoiesis

Nicola K Wilson et al. Hemasphere. .

Abstract

Hematopoiesis is one of the best studied adult stem-cell systems, with a differentiation hierarchy progressing from immature hematopoietic stem cells to over 10 distinct mature cell types. Recent technological breakthroughs now make it possible to define transcriptional profiles in thousands of individual cells. Facilitated by the wealth of prior data on cell purification and analysis strategies, hematopoiesis has been one of the earliest experimental systems to which many of these new single-cell sequencing technologies have been applied. In this review, the authors focus on recent studies, which have shed light on heterogeneity within individual populations as well as the relationships between populations, and also attempt to characterize the differences between normal and disease/perturbed states.

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Figures

Figure 1
Figure 1
Cellular heterogeneity can be resolved by single-cell molecular profiling. Classical bulk gene expression analysis generates population average measurements, which obscure any information about heterogeneity between individual cells. Importantly, cellular heterogeneity is pervasive across many biological settings, including both normal and malignant hematopoiesis. Modern single-cell molecular profiling technologies can resolve cell-to-cell heterogeneity, and thus provide new insights into normal differentiation processes and their underlying regulatory networks, cellular responses to external signals and the heterogeneous cell states present during leukemia development.
Figure 2
Figure 2
Summary of single-cell RNA sequencing methods discussed in this review. Representation of how evolving technologies are permitting the scaling of cell and transcript/gene number. Source references.,,,,,,, An average has been taken for genes/transcripts when a range was given in the original text.
Figure 3
Figure 3
The hematopoietic hierarchy in the era of single-cell gene expression analysis. The exact structure of the hematopoietic tree is still hotly debated. (i) A representation of the classical hematopoietic tree, where cells advance in a step-wise progression of differentiation and maturation, from HSCs to mature cell types. (ii) Representation of a more continuous model of differentiation based on recent studies suggesting that hematopoietic stem/progenitor cells cannot easily be resolved into specific HSC and progenitor populations. HSC, hematopoietic stem cell.,

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