Matrix Mechanosensation in the Erythroid and Megakaryocytic Lineages

Ward, Christina M.; Ravid, Katya

doi:10.3390/cells9040894

Cited by 7 publications

(5 citation statements)

References 100 publications

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“…Fibronectin-coated 44 kPa PA substrates resembling the osteoid region within the marrow cavity in particular promoted the proliferation of myeloid lineages, while laminin-coated 3.7 kPa gels resembling the sinusoid region favored erythroid lineage specification [ 7 ]. Subsequent study further corroborated the mediated role of ECM stiffness during megakaryocyte differentiation and proplatelet production [ 8 , 9 ]. These findings suggest that niche physical parameters are independent or interdependent (with chemical elements) signals that can be received by HSCPs.…”

Section: Introductionmentioning

confidence: 76%

3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment

Zhang

Gao

et al. 2022

Bioactive Materials

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Physical signals provided by the extracellular matrix (ECM) are key microenvironmental parameters for the fate decision of hematopoietic stem and progenitor cells (HSPC) in bone marrow. Insights into cell-ECM interactions are critical for advancing HSC-based tissue engineering. Herein, we employed collagen hydrogels and collagen-alginate hydrogels of defined stiffness to study the behaviors of hematopoietic progenitor cells (HPCs). Three-dimensional (3D) collagen hydrogels with a stiffness of 45 Pa were found to promote HPC maintenance and colony formation of monocyte/macrophage progenitors. Using single-cell RNA sequencing (scRNA-seq), we also characterized the comprehensive transcriptional profiles of cells randomly selected from two-dimensional (2D) and 3D hydrogels. A distinct maturation trajectory from HPCs into macrophages within the 3D microenvironment was revealed by these results. 3D-derived macrophages expressed high levels of various cytokines and chemokines, such as Saa3 , Cxcl2 , Socs3 and Tnf . Furthermore, enhanced communication between 3D-macrophages and other hematopoietic clusters based on ligand-repair interactions was demonstrated through bioinformatic analyses. Our research underlines the regulatory role of matrix-dimensionality in HPC differentiation and therefore probably be applied to the generation of specialized macrophages.

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Section: Introductionmentioning

confidence: 76%

3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment

Zhang

Gao

et al. 2022

Bioactive Materials

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“…In the BM, EMPs are able to differentiate into both erythrocytes and megakaryocytes/platelets [ 7 , 8 , 9 ]. As EMPs are the ancestors for both erythrocyte and megakaryocyte lineages, the increased number of EMPs was sufficient to result in increased erythro-megakaryopoiesis in the BM of B10.S mice after treatment with HgCl 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Erythro-megakaryopoiesis refers to the differentiation of erythrocytes and megakaryocytes/platelets, which primarily occurs in the BM after birth [ 8 ]. In the process of erythro-megakaryopoiesis, erythroid-megakaryocyte progenitors (EMPs) are capable of differentiating into both erythrocytes and megakaryocytes/platelets, with several intermediate steps including erythroid progenitors (EPs) and megakaryocyte progenitors (MkPs) [ 9 ]. EPs are comprised of two stages of progenitors, including the earlier burst-forming units-erythroid progenitors (BFU-Es) and the later colony-forming units-erythroid progenitors (CFU-Es) [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, MkPs give rise to megakaryocytes and ultimately yield platelets [ 11 ]. Erythro-megakaryopoiesis is tightly regulated in vivo, and a variety of biological factors are well known to regulate this process [ 9 ]. For instance, erythropoietin (EPO) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are able to promote erythropoiesis via the activation of the Janus kinase (Jak)2/signal transducer and activator of transcription (STAT)5 signaling pathway [ 12 , 13 , 14 , 15 ], while interferon (IFN) γ can lead to anemia partially through induction of the IFN regulatory factor (IRF)1/purine-rich nucleic acid binding protein.1 (PU.1) signaling pathway [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Mercury Chloride Impacts on the Development of Erythrocytes and Megakaryocytes in Mice

Zhao

Zhu

et al. 2021

Toxics

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Inorganic mercury (Hg2+) is a highly toxic heavy metal. The aim of this study was to investigate the impact of Hg2+ on the development of erythrocytes and megakaryocytes. B10.S mice (H-2s) and DBA/2 mice (H-2d) were administrated with 10 μM HgCl2 or 50 μM HgCl2 via drinking water for four weeks, and erythro-megakaryopoiesis was evaluated thereafter. The administration of 50 μM HgCl2 increased the number of erythrocytes and platelets in B10.S mice, which was not due to a reduced clearance for mature erythrocytes. The administration of 50 μM HgCl2, but not 10 μM HgCl2, increased the number of progenitors for erythrocytes and megakaryocytes in the bone marrow (BM) of B10.S mice, including erythroid-megakaryocyte progenitors (EMPs), burst-forming unit-erythroid progenitors (BFU-Es), colony-forming unit-erythroid progenitors (CFU-Es), and megakaryocyte progenitors (MkPs). Moreover, 50 μM HgCl2 caused EMPs to be more proliferative and possess an increased potential for differentiation into committed progenies in B10.S mice. Mechanistically, 50 μM HgCl2 increased the expression of the erythropoietin receptor (EPOR) in EMPs, thus enhancing the Jak2/STAT5 signaling pathway to promote erythro-megakaryopoiesis in B10.S mice. Conversely, 50 μM HgCl2 did not impact erythro-megakaryopoiesis in DBA/2 mice. This study may extend our current understanding for hematopoietic toxicology of Hg.

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“…48 Interestingly, the ECM stiffness can regulate mechanosensitive channels in megakaryocytes. 49 Low stiffness of the ECM increases Ca 2+ influx and consequent PI3K/ Akt (protein kinase B) signal activation through TRPV4, thereby enhancing platelet production. 50 Functional blockade of TRPV4 channels impairs platelet production.…”

Section: Trpv4 Channelmentioning

confidence: 99%

Platelet Mechanotransduction: Regulatory Cross Talk Between Mechanosensitive Receptors and Calcium Channels

Mammadova‐Bach

Gudermann

Braun

2023

ATVB

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Blood flow–induced hemodynamic changes result in mechanical stress on blood cells and vessel walls. Increased shear stress can activate platelets and other circulating cells, triggering the rapid activation of receptors, calcium channels, and related signaling mechanisms. Shear stress can also modify the folding of extracellular molecules and directly activate mechanosensitive receptors and calcium channels. The mechanical movement of the ECM (extracellular matrix) and the intracellular cortical actin cytoskeleton can change the conformation of platelet receptors and gate channel pores in the plasma membrane. Mechanosensitive platelet receptors and their downstream signaling events and metabolic products can also indirectly activate calcium channels. While the molecular composite of mechanotransduction pathways has been described in mammals, shear stress–induced platelet receptors and their cross talk with calcium channels have been incompletely characterized. In this review, we discuss current knowledge about the role of mechanosensitive platelet receptors and calcium channels in shear-dependent platelet activation and arterial thrombus formation.

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Matrix Mechanosensation in the Erythroid and Megakaryocytic Lineages

Cited by 7 publications

References 100 publications

3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment

3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment

Mercury Chloride Impacts on the Development of Erythrocytes and Megakaryocytes in Mice

Platelet Mechanotransduction: Regulatory Cross Talk Between Mechanosensitive Receptors and Calcium Channels

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