Characterization and visualization of murine coagulation factor VIII-producing cells in vivo

Hayakawa, Morisada; Sakata, Asuka; Hayakawa, Hiroko; Matsumoto, H.; Hiramoto, Takafumi; Kashiwakura, Yuji; Baatartsogt, Nemekhbayar; Fukushima, Noriyoshi; Sakata, Yoichi; Suzuki‐Inoue, Katsue; Ohmori, Tsukasa

doi:10.1038/s41598-021-94307-0

Cited by 12 publications

(6 citation statements)

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“…Recent studies using genetically engineered mice in which the enhanced green fluorescent protein (EGFP) rather than the F8 gene transcript was expressed under the regulation of the F8 locus showed that from developmental stage E12, liver sinusoidal epithelial cells (LSECs) exhibit varying amounts of EGFP, FVIII-producing LSECs being visible from the early stages of development. According to these authors, FVIII production becomes a feature of LSEC maturation as levels of LSEC EGFP increase with liver development [ 187 ].…”

Section: Clotting Factor Biosynthesismentioning

confidence: 99%

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

Pablo-Moreno

Serrano

Revuelta

et al. 2022

IJMS

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The vascular endothelium has several important functions, including hemostasis. The homeostasis of hemostasis is based on a fine balance between procoagulant and anticoagulant proteins and between fibrinolytic and antifibrinolytic ones. Coagulopathies are characterized by a mutation-induced alteration of the function of certain coagulation factors or by a disturbed balance between the mechanisms responsible for regulating coagulation. Homeostatic therapies consist in replacement and nonreplacement treatments or in the administration of antifibrinolytic agents. Rebalancing products reestablish hemostasis by inhibiting natural anticoagulant pathways. These agents include monoclonal antibodies, such as concizumab and marstacimab, which target the tissue factor pathway inhibitor; interfering RNA therapies, such as fitusiran, which targets antithrombin III; and protease inhibitors, such as serpinPC, which targets active protein C. In cases of thrombophilia (deficiency of protein C, protein S, or factor V Leiden), treatment may consist in direct oral anticoagulants, replacement therapy (plasma or recombinant ADAMTS13) in cases of a congenital deficiency of ADAMTS13, or immunomodulators (prednisone) if the thrombophilia is autoimmune. Monoclonal-antibody-based anti-vWF immunotherapy (caplacizumab) is used in the context of severe thrombophilia, regardless of the cause of the disorder. In cases of disseminated intravascular coagulation, the treatment of choice consists in administration of antifibrinolytics, all-trans-retinoic acid, and recombinant soluble human thrombomodulin.

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Section: Clotting Factor Biosynthesismentioning

confidence: 99%

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

Pablo-Moreno

Serrano

Revuelta

et al. 2022

IJMS

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“…Although the FVIII is mainly synthesized in liver sinusoidal endothelial cells (LSECs) under physiological conditions ( Shahani et al, 2014 ; Hayakawa et al, 2021 ), many studies demonstrated that the ectopic expression of FVIII in hepatocytes was efficient and the FVIII deficiency in HA mice and HA patients were rescued ( Bunting et al, 2018 ; Chen et al, 2019 ; Zhang et al, 2019 ). Successful amelioration of hemophilia A has been reported by several groups targeting the liver-expressed mouse Alb locus in vivo using AAV vectors to transfer the transgene into the liver ( Sharma et al, 2015 ; Chen et al, 2019 ; Zhang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Correction of F8 intron 1 inversion in hemophilia A patient-specific iPSCs by CRISPR/Cas9 mediated gene editing

Wu²,

Xiao³

et al. 2023

Front. Genet.

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Introduction: Hemophilia A (HA) is the most common genetic bleeding disorder caused by mutations in the F8 gene encoding coagulation factor VIII (FVIII). As the second predominant pathogenic mutation in hemophilia A severe patients, F8 Intron one inversion (Inv1) completely splits the F8 gene into two parts and disrupts the F8 transcription, resulting in no FVIII protein production. The part which contains exon 2-exon 26 covers 98% of F8 coding region.Methods: We hypothesized that in situ genetic manipulation of F8 to add a promoter and exon one before the exon two could restore the F8 expression. The donor plasmid included human alpha 1-antitrypsin (hAAT) promoter, exon one and splicing donor site (SD) based on homology-mediated end joining (HMEJ) strategy was targeted addition in hemophilia A patient-derived induced pluripotent stem cell (HA-iPSCs) using CRISPR/Cas9. The iPSCs were differentiated into hepatocyte-like cells (HPLCs).Results: The hAAT promoter and exon one were targeted addition in HA-iPSCs with a high efficiency of 10.19% via HMEJ. The FVIII expression, secretion, and activity were detected in HPLCs derived from gene-targeted iPSCs.Discussion: Thus, we firstly rescued the 140 kb reversion mutation by gene addition of a 975 bp fragment in the HA-iPSCs with Inv1 mutation, providing a promising gene correction strategy for genetic disease with large sequence variants.

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“…However, CLEC-2 is expressed at low levels in dendritic cells, neutrophils, and macrophages in mice [5,[7][8][9]. Besides blood cells, CLEC-2 is expressed at low levels in Kupffer cells and sinusoidal endothelial cells in the livers of humans and mice [5,10].…”

Section: C-type Lectin-like Receptor 2 and Platelet Activation Mechan...mentioning

confidence: 99%

A role of platelet C-type lectin-like receptor-2 and its ligand podoplanin in vascular biology

Suzuki-Inoue,

Tsukiji

2024

Current Opinion in Hematology

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Purpose of review Platelets are essential for hemostasis and are also vital in lymphatic and lung development and the maintenance of vascular integrity. Platelet activation receptor C-type lectin-like receptor 2 (CLEC-2) and its endogenous ligand podoplanin (PDPN) in lymphatic endothelial cells (LECs) and other cells regulate these processes. This review aims to comprehensively summarize the roles of platelet CLEC-2 and PDPN. This review also focuses on discussing the underlying mechanisms by which platelet CLEC-2 and PDPN mediate blood/lymphatic separation. Findings CLEC-2/PDPN-induced platelet activation in the primary lymph sacs, developmental lymphovenous junctions, neonatal mesentery, and the site of tumor lymphangiogenesis prevents blood/lymphatic vessel misconnection. Further, CLEC-2/PDPN-induced platelet activation is essential for lung development. Mice deficient in CLEC-2 or PDPN show blood-filled lymphatics, lung malformations, and cerebrovascular abnormalities. CLEC-2 deletion in steady-state adult mice did not result in blood/lymphatic vessel mixing. In adulthood, CLEC-2 maintains vascular integrity and that of high endothelial venules in lymph nodes. CLEC-2 deletion in adulthood results in hemorrhage under inflammatory conditions, and hemolymph nodes. Summary The platelet CLEC-2/LEC PDPN interaction prevents blood/lymphatic vessel mixing at active remodeling sites of the blood/lymphatic system, but not in steady-state adult mice. This interaction also regulates vascular integrity when vascular permeability increases before and after birth.

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Characterization and visualization of murine coagulation factor VIII-producing cells in vivo

Cited by 12 publications

References 50 publications

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

Correction of F8 intron 1 inversion in hemophilia A patient-specific iPSCs by CRISPR/Cas9 mediated gene editing

A role of platelet C-type lectin-like receptor-2 and its ligand podoplanin in vascular biology

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