Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes

Liu, Cuicui; Wu, Dan; Xia, Meijuan; Li, Minmin; Sun, Zhiqiang; Shen, Biao; Liu, Yiying; Jiang, Erlie; Wang, Hongtao; Su, Pei; Shi, Lihong; Xiao, Zhijian; Zhu, Xiaofan; Zhou, Wen; Wang, Qian-fei; Gào, Xin; Cheng, Tao; Zhou, Jiaxi

doi:10.1002/advs.202100921

Cited by 40 publications

(60 citation statements)

References 55 publications

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“…MK5 enriched cell migration and immune response genes (Figure 1C, D; Figure 1-figure supplement 4A-E), cytokine, chemokine (Figure 1E, F; Figure 1-figure supplement 4F), and genes involved in immune cell interaction (Figure 1G, Figure 1-figure supplement 5A). MK5 also expressed signature genes in recently reported inflammatory-related MKs (Cd53, Lsp1, Anxa1, Spi) (Sun et al, 2021) and immune MKs (Ccl3, Cd52, Selplg, Sell, Adam8) (Liu et al, 2021) (Figure 1- figure supplement 5B). We also noticed that MK5 highly expressed Cxcr4 than other MK subpopulations (Figure 1H, I), although most MKs express CXCR4 (Hamada et al, 1998) (Figure 1-figure supplement 6A).…”

Section: Resultsmentioning

confidence: 57%

“…Therefore, we re-clustered the transcriptionally enriched 1712 MKs into five subpopulations, termed MK1 to MK5 (Figure 1B; Figure 1-figure supplement 3A, B), which were further confirmed by the integrated scRNA-seq analysis platform to rule out the potential immune cell contamination (Pariser et al, 2021; Xie et al, 2020; Yeung et al, 2020) (Figure 1-figure supplement 3C, D). However, we noticed that mature MKs with huge sizes were captured at a relatively low rate, potentially due to the limitation in current techniques in cell purification and single-cell preparation (Liu et al, 2021; Sun et al, 2021). Enriched signature genes in Gene Ontology exhibited that MK1 and MK2 highly expressed nuclear division, DNA replication and repair genes for endomitosis (Figure 1C, D).…”

Section: Resultsmentioning

confidence: 99%

“…Accordingly, MKs prevent the spread of dengue virus infection by enhancing the type 1 interferons pathway in murine and clinical biospecimens (Campbell et al, 2019) and contribute to cytokine storms in severe COVID-19 patients (Bernardes et al, 2020; Ren et al, 2021; Stephenson et al, 2021). Recent scRNA-seq studies suggested the existence of MK subpopulations for inflammation responses (Liu et al, 2021; Pariser et al, 2021; Sun et al, 2021; Wang et al, 2021); however, the mechanism that MKs regulate immune response remains elusive. Here, we identified that MK5 has both MK and immune cell characteristics, producing platelets and enriching immune response genes.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the recent single-cell atlas shows that MKs are heterogeneous and contain subpopulations that express multiple immune genes and are involved in inflammation response (Liu et al, 2021;Pariser et al, 2021;Sun et al, 2021;Yeung et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Lung MKs contribute to thrombosis (Lefrancais et al, 2017) and, more interestingly, participate in immune responses (Pariser et al, 2021), although the relationship between lung MKs and bone marrow circulating MKs (Nishimura et al, 2015) remains unexplored. Furthermore, the recent single-cell atlas shows that MKs are heterogeneous and contain subpopulations that express multiple immune genes and are involved in inflammation response (Liu et al, 2021; Pariser et al, 2021; Sun et al, 2021; Yeung et al, 2020). However, the mechanisms that MK subpopulations regulate immune cells against bacterial pathogens remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Megakaryocyte derived immune-stimulating cells regulate host-defense immunity against bacterial pathogens

Wang

Xie

Han

et al. 2021

Preprint

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Megakaryocytes (MKs) continuously produce platelets in bone marrow to support hemostasis. However, MKs also play roles beyond thrombopoiesis as they regulate hematopoietic stem cell quiescence and erythropoiesis, which suggests the functional heterogeneity of MKs. Here, using single-cell sequencing we identified an MK-derived immune-stimulating cell (MDIC) population, which plays an important role in host-protective response against bacteria. In contrast to platelet-generating MKs, MDICs highly express cell migration, immune-modulatory, and response genes. Upon Listeria (L.) monocytogenes infection, MDICs egress to circulation and infiltrate into the spleen, liver and lung. MDICs interact with myeloid cells to promote their migration and tissue infiltration. More importantly, MDICs stimulate phagocytosis of macrophages and neutrophils by producing TNFα and IL-6 and facilitating antigen-specific T cell activation via IL-6 to enhance anti-bacterial response. Ablation of MKs reduced innate immune response and compromised T cell activation in spleen and liver, impairs the anti-bacterial effects in mice under L. monocytogenes challenge. Finally, infection-induced emergency megakaryopoiesis efficiently stimulated MDICs generation upon bacterial infection. Overall, we identify MDICs as a novel MK subpopulation, which regulates host-defense immune response against bacterial infection.

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Section: Resultsmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Megakaryocyte derived immune-stimulating cells regulate host-defense immunity against bacterial pathogens

Wang

Xie

Han

et al. 2021

Preprint

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Three‐dimensional spatial mapping of the human hematopoietic microenvironment in healthy and diseased bone marrow

Bräunig

Karmhag

et al. 2023

Cytometry Pt A

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The bone marrow hematopoietic microenvironment (HME) plays a pivotal role in regulating normal and diseased hematopoiesis. However, the spatial organization of the human HME has not been thoroughly investigated yet. Therefore, we developed a three‐dimensional (3D) immunofluorescence model to analyze changes in the cellular architecture in control and diseased bone marrows (BMs). BM biopsies from patients with myeloproliferative neoplasms (MPNs) were stained sequentially for CD31, CD34, CD45, and CD271 with repetitive bleaching steps to realize five color images with DAPI as a nuclear stain. Hematopoietically normal age‐matched BM biopsies served as controls. Twelve subsequent slides per sample were stacked to create three‐dimensional bone marrow reconstructions with the imaging program Arivis Visions 4D. Iso‐surfaces for niche cells and structures were created and exported as mesh objects for spatial distribution analysis in the 3D creation suite Blender. We recapitulated the bone marrow architecture using this approach and produced comprehensive 3D models of endosteal and perivascular BM niches. MPN bone marrows displayed apparent differences compared to the controls, especially concerning CD271 staining density, megakaryocyte (MK) morphology, and distribution. Furthermore, measurements of the spatial relationships of MKs and hematopoietic stem and progenitor cells with vessels and bone structures in their corresponding niche environments revealed the most pronounced differences in the vascular nice in polycythemia vera. Taken together, using a repetitive staining and bleaching approach allowed us to establish a 5‐color analysis of human BM biopsies, which is difficult to achieve with conventional staining approaches. Based on this, we generated 3D BM models which recapitulated key pathological features and, importantly, allowed us to define the spatial relationships between different bone marrow cell types. We, therefore, believe that our method can provide new and valuable insights into bone marrow cellular interaction research.

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Illustrated State‐of‐the‐Art Capsules of the ISTH 2022 Congress

Ariëns

Hunt

Agbani

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020.Readers are also welcome to utilize capsules for teaching and ongoing education.

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Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes

Cited by 40 publications

References 55 publications

Megakaryocyte derived immune-stimulating cells regulate host-defense immunity against bacterial pathogens

Megakaryocyte derived immune-stimulating cells regulate host-defense immunity against bacterial pathogens

Three‐dimensional spatial mapping of the human hematopoietic microenvironment in healthy and diseased bone marrow

Illustrated State‐of‐the‐Art Capsules of the ISTH 2022 Congress

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