Biological Characteristics and Regulation of Early Megakaryocytopoiesis

Yang, Jae Wook; Zhao, Song; Ma, Dongchu

doi:10.1007/s12015-019-09905-3

Cited by 6 publications

(7 citation statements)

References 80 publications

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“…Moreover, the ROS generation could play pivotal roles in regulating the megakaryocyte differentiation (Chen et al, 2013;Yang et al, 2019). In the present study, the elevation in cellular ROS level due to TMEA treatment, confirming the differentiation and maturation of TMEA-induced megakaryocytes were accompanied by the increase of ROS.…”

Section: Discussionsupporting

confidence: 81%

“…ROS generation could play pivotal roles in regulating the differentiation of megakaryocytes (Yang et al, 2019). The results from flow cytometry assay using DCFH-DA probe showed that TMEA induced excessive ROS production in megakaryocytes on the 8th and 12th days (Figure 8A),which was in a concentration-dependent manner (Figure 8C).…”

Section: Reactive Oxygen Species (Ros) Levelmentioning

confidence: 95%

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Section: Discussionsupporting

confidence: 81%

Section: Reactive Oxygen Species (Ros) Levelmentioning

confidence: 95%

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“…We demonstrated that CREG1 deficiency impaired platelet production, along with decreased platelet counts and a compensatory upregulation of megakaryopoiesis. Megakaryocytes are derived from hematopoietic stem cells through hierarchical differentiation, after the hematopoietic stem cells are differentiated into megakaryocytic progenitor cells, they eventually form megakaryocytes through proliferation and terminal differentiation 27 , 28 . Previous studies have reported that CREG1 can induce smooth muscle, cardiomyogenic, and endothelial differentiation from embryonic stem cells.…”

Section: Discussionmentioning

confidence: 99%

The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis

Song¹,

Li²,

Peng³

et al. 2023

Int. J. Biol. Sci.

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Abnormal megakaryocyte maturation and platelet production lead to platelet-related diseases and impact the dynamic balance between hemostasis and bleeding. Cellular repressor of E1A-stimulated gene 1 (CREG1) is a glycoprotein that promotes tissue differentiation. However, its role in megakaryocytes remains unclear. In this study, we found that CREG1 protein is expressed in platelets and megakaryocytes and was decreased in the platelets of patients with thrombocytopenia. A cytosine arabinoside-induced thrombocytopenia mouse model was established, and the mRNA and protein expression levels of CREG1 were found to be reduced in megakaryocytes. We established megakaryocyte/platelet conditional knockout (Creg1 pf4-cre ) and transgenic mice (tg-Creg1). Compared to Creg1 fl/fl mice, Creg1 pf4-cre mice exhibited thrombocytopenia, which was mainly caused by inefficient bone marrow (BM) thrombocytopoiesis, but not by apoptosis of circulating platelets. Cultured Creg1 pf4-cre -megakaryocytes exhibited impairment of the actin cytoskeleton, with less filamentous actin, significantly fewer proplatelets, and lower ploidy. CREG1 directly interacts with MEK1/2 and promotes MEK1/2 phosphorylation. Thus, our study uncovered the role of CREG1 in the regulation of megakaryocyte maturation and thrombopoiesis, and it provides a possible theoretical basis for the prevention and treatment of thrombocytopenia.

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“…The mitochondrial OXPHOS plays important role in the hematopoiesis process [ 30 , 31 ]. Recent researches have shown that mitochondrial activity or content determines the status of hematopoietic stem cells (HSCs), the source of the megakaryocytes, [ 32 ] and mitochondrial membrane potential (MPP) can influence the transcription rate of HSCs [ 45 ]. Quiescent and self-renewing HSCs rely on mitochondrial OXPHOS rather than on glycolysis for energy production, thus metabolically rewiring from glycolysis to mitochondrial-based energy generation accompanying with HSC differentiation and lineage commitment [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Airborne particulate matters induce thrombopoiesis from megakaryocytes through regulating mitochondrial oxidative phosphorylation

Jin

Wang

et al. 2021

Part Fibre Toxicol

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Background Although airborne fine particulate matter (PM) pollution has been demonstrated as an independent risk factor for pulmonary and cardiovascular diseases, their currently-available toxicological data is still far from sufficient to explain the cause-and-effect. Platelets can regulate a variety of physiological and pathological processes, and the epidemiological study has indicated a positive association between PM exposure and the increased number of circulative platelets. As one of the target organs for PM pollution, the lung has been found to be involved in the storage of platelet progenitor cells (i.e. megakaryocytes) and thrombopoiesis. Whether PM exposure influences thrombopoiesis or not is thus explored in the present study by investigating the differentiation of megakaryocytes upon PM treatment. Results The results showed that PM exposure promoted the thrombopoiesis in an exposure concentration-dependent manner. PM exposure induced the megakaryocytic maturation and development by causing cell morphological changes, occurrence of DNA ploidy, and alteration in the expressions of biomarkers for platelet formation. The proteomics assay demonstrated that the main metabolic pathway regulating PM-incurred alteration of megakaryocytic maturation and thrombopoiesis was the mitochondrial oxidative phosphorylation (OXPHOS) process. Furthermore, airborne PM sample promoted-thrombopoiesis from megakaryocytes was related to particle size, but independent of sampling filters. Conclusion The findings for the first time unveil the potential perturbation of haze exposure in thrombopoiesis from megakaryocytes by regulating mitochondrial OXPHOS. The substantial evidence on haze particle-incurred hematotoxicity obtained herein provided new insights for assessing the hazardous health risks from PM pollution.

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Biological Characteristics and Regulation of Early Megakaryocytopoiesis

Cited by 6 publications

References 80 publications

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The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis

Airborne particulate matters induce thrombopoiesis from megakaryocytes through regulating mitochondrial oxidative phosphorylation

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