Large‐Scale Generation of Megakaryocytes from Human Embryonic Stem Cells Using Transgene‐Free and Stepwise Defined Suspension Culture Conditions

Scientists defined an optimal, stepwise and completely xeno‐free culture protocol for the generation of megakaryocytes from human embryonic stem cells.
[Cell Proliferation]
Zhang, B., Wu, X., Zi, G., He, L., Wang, S., Chen, L., Fan, Z., Nan, X., Xi, J., Yue, W., Wang, L., Wang, L., Hao, J., Pei, X., & Li, Y. (n.d.). Large-scale generation of megakaryocytes from human embryonic stem cells using transgene-free and stepwise defined suspension culture conditions. Cell Proliferation, n/a(n/a), e13002. https://doi.org/https://doi.org/10.1111/cpr.13002 Cite
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Hematopoietic Stem Cell Heterogeneity Is Linked to the Initiation and Therapeutic Response of Myeloproliferative Neoplasms

Single-cell gene expression profiling with parallel mutation detection demonstrated that the megakaryocyte-primed hematopoietic stem cells subpopulation expanded significantly with enhanced potential in untreated individuals with JAK2V617F+essential thrombocythemia, driven primarily by the JAK2 mutation and elevated interferon signaling.
[Cell Stem Cell]
Tong, J., Sun, T., Ma, S., Zhao, Y., Ju, M., Gao, Y., Zhu, P., Tan, P., Fu, R., Zhang, A., Wang, D., Wang, D., Xiao, Z., Zhou, J., Yang, R., Loughran, S. J., Li, J., Green, A. R., Bresnick, E. H., … Shi, L. (2021). Hematopoietic Stem Cell Heterogeneity Is Linked to the Initiation and Therapeutic Response of Myeloproliferative Neoplasms. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2021.01.018 Cite
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15-PGDH Inhibition Activates the Splenic Niche to Promote Hematopoietic Regeneration

The authors demonstratef that the splenic microenvironment, specifically 15-PGDH high-expressing macrophages, megakaryocytes, and mast cells, regulated steady-state hematopoiesis and potentiated recovery after bone-marrow transplantation.
[JCI Insight]
Smith, J. N. P., Dawson, D. M., Christo, K. F., Jogasuria, A. P., Cameron, M. J., Antczak, M. I., Ready, J. M., Gerson, S. L., Markowitz, S. D., & Desai, A. B. (2021). 15-PGDH inhibition activates the splenic niche to promote hematopoietic regeneration. JCI Insight. https://doi.org/10.1172/jci.insight.143658 Cite
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Sequence-Specific 2′-O-Methoxyethyl Antisense Oligonucleotides Activate Human Platelets through Glycoprotein VI, Triggering Formation of Plateletleukocyte Aggregates

Human cord blood-derived megakaryocytes were treated with antisense oligonucleotides (ASOs) to study effects on proplatelet production. Platelet activation and platelet-leukocyte aggregates were analyzed in ASO-treated blood from healthy human volunteers.
[Haematologica]
Slingsby, M. H. L., Vijey, P., Tsai, I.-T., Roweth, H., Couldwell, G., Wilkie, A. R., Gaus, H., Goolsby, J. M., Okazaki, R., Terkovich, B. E., Semple, J. W., Thon, J. N., Henry, S. P., Narayanan, P., & Jr, J. E. I. (2020). Sequence-specific 2’-O-methoxyethyl antisense oligonucleotides activate human platelets through glycoprotein VI, triggering formation of plateletleukocyte aggregates. Haematologica. https://doi.org/10.3324/haematol.2020.260059 Cite
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Metabolic Sensor O‐GlcNAcylation Regulates Megakaryopoiesis and Thrombopoiesis through c‐Myc Stabilization and Integrin Perturbation

Scientists revealed for the first time that cellular O‐GlcNAcylation levels declined along the course of megakaryocyte differentiation from human‐derived hematopoietic stem and progenitor cells.
[Stem Cells]
Luanpitpong, S., Poohadsuan, J., Klaihmon, P., Kang, X., Tangkiettrakul, K., & Issaragrisil, S. (n.d.). Metabolic sensor O-GlcNAcylation regulates megakaryopoiesis and thrombopoiesis through c-Myc stabilization and integrin perturbation. STEM CELLS, n/a(n/a). https://doi.org/https://doi.org/10.1002/stem.3349 Cite
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COVID-19 Immune Features Revealed by a Large-Scale Single Cell Transcriptome Atlas

Scientists applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. SARS-CoV-2 RNAs were found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within viral positive cells.
[Cell]
Ren, X., Wen, W., Fan, X., Hou, W., Su, B., Cai, P., Li, J., Liu, Y., Tang, F., Zhang, F., Yang, Y., He, J., Ma, W., He, J., Wang, P., Cao, Q., Chen, F., Chen, Y., Cheng, X., … Zhang, Z. (2021). COVID-19 immune features revealed by a large-scale single cell transcriptome atlas. Cell, 0(0). https://doi.org/10.1016/j.cell.2021.01.053 Cite
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The Necroptotic Cell Death Pathway Operates in Megakaryocytes, but Not in Platelet Synthesis

The authors demonstrated that megakaryocytes possess a functional necroptosis signalling cascade. Necroptosis activation led to phosphorylation of mixed lineage kinase domain-like, loss of viability and cell swelling.
[Cell Death & Disease]
Moujalled, D., Gangatirkar, P., Kauppi, M., Corbin, J., Lebois, M., Murphy, J. M., Lalaoui, N., Hildebrand, J. M., Silke, J., Alexander, W. S., & Josefsson, E. C. (2021). The necroptotic cell death pathway operates in megakaryocytes, but not in platelet synthesis. Cell Death & Disease, 12(1), 1–17. https://doi.org/10.1038/s41419-021-03418-z Cite
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Generation and Manipulation of Human iPSC-Derived Platelets

The authors focus on the current status of the development, application and manipulation of iPSC-derived platelet-like particles, which has been leading the field of regenerative medicine using iPSC-derived blood cells and has reached the first-in-human clinical trial.
[Cellular and Molecular Life Sciences]
Sugimoto, N., & Eto, K. (2021). Generation and manipulation of human iPSC-derived platelets. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-020-03749-8 Cite
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Evaluation of Angiogenic Signaling Molecules Associated with Reactive Thrombocytosis in an Iron-Deficient Rat Model

A review of the bone marrow showed an increase in the number of megakaryocytes, vascular structures, as well as increased intensity of stain for VEGF, and CXC chemokine receptor 4 in rats with iron deficiency anemia compared to controls.
[Pediatric Research]
Garcia, J., Mankin, P., Gnanamony, M., & de Alarcon, P. A. (2021). Evaluation of angiogenic signaling molecules associated with reactive thrombocytosis in an iron-deficient rat model. Pediatric Research, 1–6. https://doi.org/10.1038/s41390-020-01318-0 Cite
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Post-Translational Polymodification of β1-Tubulin Regulates Motor Protein Localization in Platelet Production and Function

Researchers found distinct patterns of polymodification in megakaryocytes and platelets, mediated by the antagonistic activities of the cell specific expression of tubulin tyrosine ligase like and cytosolic carboxypeptidase enzymes.
[Haematologica]
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Decoding Human Megakaryocyte Development

The authors used single-cell RNA sequencing of human megakaryocytes from embryonic yolk sac and fetal liver to characterize the transcriptome, cellular heterogeneity, and developmental trajectories of early megakaryopoiesis.
[Cell Stem Cell]
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