New Insights Into the Differentiation of Megakaryocytes From Hematopoietic Progenitors

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2019 May 3

PMID 31043076

Citations 119

Authors

Leila J Noetzli

Shauna L French

Kellie R Machlus

Affiliations

Soon will be listed here.

Abstract

Megakaryocytes are hematopoietic cells, which are responsible for the production of blood platelets. The traditional view of megakaryopoiesis describes the cellular journey from hematopoietic stem cells, through a hierarchical series of progenitor cells, ultimately to a mature megakaryocyte. Once mature, the megakaryocyte then undergoes a terminal maturation process involving multiple rounds of endomitosis and cytoplasmic restructuring to allow platelet formation. However, recent studies have begun to redefine this hierarchy and shed new light on alternative routes by which hematopoietic stem cells are differentiated into megakaryocytes. In particular, the origin of megakaryocytes, including the existence and hierarchy of megakaryocyte progenitors, has been redefined, as new studies are suggesting that hematopoietic stem cells originate as megakaryocyte-primed and can bypass traditional lineage checkpoints. Overall, it is becoming evident that megakaryopoiesis does not only occur as a stepwise process, but is dynamic and adaptive to biological needs. In this review, we will reexamine the canonical dogmas of megakaryopoiesis and provide an updated framework for interpreting the roles of traditional pathways in the context of new megakaryocyte biology. Visual Overview- An online visual overview is available for this article.

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References

Schwer H, Lecine P, Tiwari S, Italiano Jr J, Hartwig J, Shivdasani R . A lineage-restricted and divergent beta-tubulin isoform is essential for the biogenesis, structure and function of blood platelets. Curr Biol. 2001; 11(8):579-86. DOI: 10.1016/s0960-9822(01)00153-1. View

Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M . Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-6. DOI: 10.1038/nature02040. View

Athanasiou M, Mavrothalassitis G, Blair D . FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells. Leukemia. 2000; 14(3):439-45. DOI: 10.1038/sj.leu.2401689. View

Gruneboom A, Hawwari I, Weidner D, Culemann S, Muller S, Henneberg S . A network of trans-cortical capillaries as mainstay for blood circulation in long bones. Nat Metab. 2019; 1(2):236-250. PMC: 6795552. DOI: 10.1038/s42255-018-0016-5. View

Machlus K, Johnson K, Kulenthirarajan R, Forward J, Tippy M, Soussou T . CCL5 derived from platelets increases megakaryocyte proplatelet formation. Blood. 2015; 127(7):921-6. PMC: 4760093. DOI: 10.1182/blood-2015-05-644583. View

McCarty J, Sprugel K, Fox N, Sabath D, Kaushansky K . Murine thrombopoietin mRNA levels are modulated by platelet count. Blood. 1995; 86(10):3668-75. View

Shivdasani R, Rosenblatt M, Zucker-Franklin D, Jackson C, Hunt P, Saris C . Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell. 1995; 81(5):695-704. DOI: 10.1016/0092-8674(95)90531-6. View

Sullenbarger B, Bahng J, Gruner R, Kotov N, Lasky L . Prolonged continuous in vitro human platelet production using three-dimensional scaffolds. Exp Hematol. 2008; 37(1):101-10. PMC: 2676426. DOI: 10.1016/j.exphem.2008.09.009. View

Haas S, Hansson J, Klimmeck D, Loeffler D, Velten L, Uckelmann H . Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors. Cell Stem Cell. 2015; 17(4):422-34. DOI: 10.1016/j.stem.2015.07.007. View

10.

Boilard E, Nigrovic P, Larabee K, Watts G, Coblyn J, Weinblatt M . Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science. 2010; 327(5965):580-3. PMC: 2927861. DOI: 10.1126/science.1181928. View

11.

Zhu F, Feng M, Sinha R, Seita J, Mori Y, Weissman I . Screening for genes that regulate the differentiation of human megakaryocytic lineage cells. Proc Natl Acad Sci U S A. 2018; 115(40):E9308-E9316. PMC: 6176640. DOI: 10.1073/pnas.1805434115. View

12.

Ikonomi P, Noguchi C, Miller W, Kassahun H, Hardison R, Schechter A . Levels of GATA-1/GATA-2 transcription factors modulate expression of embryonic and fetal hemoglobins. Gene. 2001; 261(2):277-87. DOI: 10.1016/s0378-1119(00)00510-2. View

13.

Nichols K, Crispino J, Poncz M, White J, Orkin S, Maris J . Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet. 2000; 24(3):266-70. PMC: 10576470. DOI: 10.1038/73480. View

14.

Lu Y, Sanada C, Xavier-Ferrucio J, Wang L, Zhang P, Grimes H . The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell Rep. 2018; 25(8):2083-2093.e4. PMC: 6336197. DOI: 10.1016/j.celrep.2018.10.084. View

15.

Hirao A, Arai F, Suda T . Regulation of cell cycle in hematopoietic stem cells by the niche. Cell Cycle. 2004; 3(12):1481-3. DOI: 10.4161/cc.3.12.1281. View

16.

Long M, Briddell R, Walter A, Bruno E, Hoffman R . Human hematopoietic stem cell adherence to cytokines and matrix molecules. J Clin Invest. 1992; 90(1):251-5. PMC: 443088. DOI: 10.1172/JCI115844. View

17.

EBAUGH Jr F, Bird R . The normal megakaryocyte concentration in aspirated human bone marrow. Blood. 1951; 6(1):75-80. View

18.

Yamada M, Komatsu N, Okada K, Kato T, Miyazaki H, Miura Y . Thrombopoietin induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in a human thrombopoietin-dependent cell line. Biochem Biophys Res Commun. 1995; 217(1):230-7. DOI: 10.1006/bbrc.1995.2768. View

19.

Chitteti B, Kacena M, Voytik-Harbin S, Srour E . Modulation of hematopoietic progenitor cell fate in vitro by varying collagen oligomer matrix stiffness in the presence or absence of osteoblasts. J Immunol Methods. 2015; 425:108-113. DOI: 10.1016/j.jim.2015.07.001. View

20.

Kaushansky K, Lok S, Holly R, Broudy V, Lin N, BAILEY M . Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature. 1994; 369(6481):568-71. DOI: 10.1038/369568a0. View