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Review
. 2018 Sep 11;2(17):2273-2281.
doi: 10.1182/bloodadvances.2018019539.

Deciphering the differentiation trajectory from hematopoietic stem cells to mast cells

Jennine Grootens  1   2 , Johanna S Ungerstedt  3   4 , Gunnar Nilsson  1   2   5   6 , Joakim S Dahlin  1   2
Affiliations
Review

Deciphering the differentiation trajectory from hematopoietic stem cells to mast cells

Jennine Grootens et al. Blood Adv. .

Abstract

Hematopoietic stem cells differentiate into all types of blood cells, including peripheral tissue-resident mast cells. The early mast cell differentiation takes place in the bone marrow, after which the progenitor cells enter the circulation and mature once reaching their target organ. Early results from single-cell culture experiments and colony-forming assays have produced the classic hierarchical tree model of hematopoiesis. The introduction of high-throughput, single-cell RNA sequencing is now revolutionizing our understanding of the differentiation process, questioning the classic tree-based models. By integrating the results from early cell culture experiments with single-cell transcriptomics, we present a differentiation landscape model of hematopoiesis and discuss it with focus on mast cells. The review also describes how the hematologic neoplasm systemic mastocytosis can be used to model human hematopoiesis using naturally occurring cell barcoding by means of the common KIT D816V mutation.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Evolution of models describing hematopoiesis. (A) Classic hierarchical model of hematopoiesis. (B) Revised model of hematopoiesis with LMPPs and BMCPs. (C) Differentiation landscape model of hematopoiesis. Hematopoietic stem and progenitor cells differentiate along ≥1 trajectories in the landscape. Each arm represents the entry point to 1 lineage, with the exception of the HSC arm, which is the starting point. Previously described bi- and multipotent progenitors are indicated, but the model is flexible and allows for tripotent erythroid, mast cell, and basophil progenitors, for example. This model focuses on myeloerythroid cell differentiation; the multiple lymphoid populations that exist are therefore not described in detail. Ba, basophil; CLP, common lymphoid progenitor; Eo, eosinophil; Ery, erythrocyte; HSC, hematopoietic stem cell; lymph, lymphocyte; MC, mast cell; Meg, megakaryocyte; mono, monocytes; MPP, multipotent progenitor; Neu, neutrophil.
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