Brief Report: Single-Cell Analysis Reveals Cell Division-Independent Emergence of Megakaryocytes From Phenotypic Hematopoietic Stem Cells

Roch, Aline; Trachsel, Vincent

doi:10.1002/stem.2106

Cited by 34 publications

(28 citation statements)

References 27 publications

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“…Thus, further assays are needed to determine if this is an HSC now limited to Mk, or an Mk-progenitor gaining CD41 expression in response to stress signals induced by LPS. The possibility that Mk progenitors are not derived from HSCs but simply share an identical surface marker pattern was also raised by Roch et al [35] who observed that 15% of single HSCs (LSK CD150+CD48−CD34−) directly differentiate to megakaryocytes without cell division. [35] In either case, these progenitors could be unique in their ability to serve as an emergency pool for platelet production in response to inflammatory insults, [36] and would be consistent with the hypothesis that platelets, which are extremely important in response to injury and inflammation, have more than one production route.…”

Section: Alternatives To the Megakaryocytic-erythroid Progenitor (Mepmentioning

confidence: 99%

Concise Review: Bipotent Megakaryocytic-Erythroid Progenitors: Concepts and Controversies

Xavier-Ferrucio

Krause

2018

Stem Cells

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Hematopoietic stem and progenitor cells maintain blood formation throughout our lifetime by undergoing long- and short-term self-renewal, respectively. As progenitor cells progress through the hematopoiesis process, their differentiation capabilities narrow, such that the precursors become committed to only one or two lineages. This Review focuses on recent advances in the identification and characterization of bipotent megakaryocytic-erythroid progenitors (MEP), the cells that can further produce two completely different functional outputs: platelets and red blood cells. The existence of MEP has sparked controversy as studies describing the requirement for this intermediate progenitor stage prior to commitment to the erythroid and megakaryocytic lineages have been potentially contradictory. Interpretation of these studies is complicated by the variety of species, cell sources, and analytical approaches used along with inherent challenges in the continuum of hematopoiesis, where hematopoietic progenitors do not stop at discrete steps on single paths as classically drawn in hematopoietic hierarchy models. With the goal of improving our understanding of human hematopoiesis, we discuss findings in both human and murine cells. Based on these data, MEP clearly represent a transitional stage of differentiation in at least one route to the generation of both megakaryocytes and erythroid cells. Stem Cells 2018;36:1138-1145.

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Section: Alternatives To the Megakaryocytic-erythroid Progenitor (Mepmentioning

confidence: 99%

Concise Review: Bipotent Megakaryocytic-Erythroid Progenitors: Concepts and Controversies

Xavier-Ferrucio

Krause

2018

Stem Cells

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“…Indeed, 10%-15% of the highly purified LT-HSC population can directly differentiate into Mgk without cell division in single-cell in vitro culture. The same population also includes highly proliferating cells producing 100-1,000 singlelineage Mgks [16,25,28]. Furthermore, the paired daughter assay shows Mgks can be differentiated from HSCs even at the first cell division [25].…”

Section: Mgk Lineage Commitment Within the Hsc Compartmentmentioning

confidence: 99%

The Road Map for Megakaryopoietic Lineage from Hematopoietic Stem/Progenitor Cells

Nishikii

Naoki

2017

Stem Cells Translational Medicine

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SummaryMegakaryocytes (Mgks) are terminally differentiated blood cells specified to produce platelets, whereas hematopoietic stem cells (HSCs) are the most undifferentiated blood cells that retain multipotency to produce all kinds of blood cells. As such, these two cell types reside at the bottom and the top of the hematopoietic hierarchy, respectively. In spite of this distance, they share several important cell surface molecules as well as transcription factors.In the conventional step‐wise differentiation model, HSCs gradually lose their self‐renewal capacity and differentiate into multipotent progenitors (MPPs), which is the first branch point of myeloid and lymphoid lineage. In this model, common myeloid progenitors can differentiate into bipotent Mgk/erythroid progenitors (MEPs), and MEPs eventually differentiate into unipotent mature Mgks. However, it has been recently reported that a subpopulation within the HSC and MPP compartments demonstrates an Mgk‐biased differentiation potential. These reports imply that revisions to the HSC‐to‐Mgk differentiation pathway should be discussed. In this review, we summarize recent findings about Mgk differentiation from HSCs and discuss future directions in this research field. Stem Cells Translational Medicine 2017;6:1661–1665

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“…Recent advances in single-cell technologies including single-cell transplantation and lineage tracing studies of unperturbed hematopoiesis have revealed that hematopoiesis occurs over a continuum rather than via distinct, oligopotent intermediate steps (Laurenti and Gottgens, 2018;Psaila and Mead, 2019;Velten et al, 2017), and also that a proportion of HSCs, at least in the murine system, are megakaryocyte-biased but retain capacity for multilineage reconstitution (Adolfsson et al, 2005;Benz et al, 2012;Carrelha et al, 2018;Rodriguez-Fraticelli et al, 2018;Sanjuan-Pla et al, 2013;Shin et al, 2014). Lineage-committed megakaryocytes arising directly from HSCs, sometimes without cell division, have also been reported (Notta et al, 2016;Roch et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

Psaila

Wang

Rodríguez-Meira

et al. 2019

Preprint

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Myelofibrosis is a severe myeloproliferative neoplasm characterised by increased numbers of abnormal bone marrow megakaryocytes that induce progressive fibrosis, destroying the hematopoietic microenvironment. To determine the cellular and molecular basis for aberrant megakaryopoiesis in myelofibrosis, we performed high-throughput single-cell transcriptome profiling of 50,538 hematopoietic stem/progenitor cells (HSPCs), single-cell proteomics, genomics and functional assays. We identified an aberrant pathway for direct megakaryocyte differentiation from the earliest stages of hematopoiesis in myelofibrosis and associated aberrant molecular signatures, including surface antigens selectively expressed by JAK2-mutant HSPCs. Myelofibrosis megakaryocyte progenitors were heterogeneous, with distinct expression of fibrosis and proliferation-associated genes and putative therapy targets. We validated the immunoglobulin receptor G6B as a promising JAK2-mutant clone-specific antigen warranting further development as 2 an immunotherapy target. Our study paves the way for selective targeting of the myelofibrosis clone and more broadly illustrates the power of single-cell multi-omics to discover tumor-specific therapeutic targets and mediators of tissue fibrosis.

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Brief Report: Single-Cell Analysis Reveals Cell Division-Independent Emergence of Megakaryocytes From Phenotypic Hematopoietic Stem Cells

Cited by 34 publications

References 27 publications

Concise Review: Bipotent Megakaryocytic-Erythroid Progenitors: Concepts and Controversies

Concise Review: Bipotent Megakaryocytic-Erythroid Progenitors: Concepts and Controversies

The Road Map for Megakaryopoietic Lineage from Hematopoietic Stem/Progenitor Cells

Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

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