Regulation of platelet numbers and sizes by signaling pathways.

Platelets
Jaturawat PawinwongchaiPonlapat Rojnuckarin

Abstract

Either the glycoprotein (GP) Ib deficiency or hyper-function in humans can cause macrothrombocytopenia, the molecular mechanisms of which remain unclear. Herein, the investigations for disease pathogenesis were performed in the human induced pluripotent stem cell (hiPSC) model. The hiPSCs carrying a gain-of-function GP1BA p.M255V mutation which was described in platelet-type von Willebrand disease (PT-VWD) were generated using CRISPR/Cas9. The GP1BA-null hiPSCs were previously derived from a Bernard-Soulier syndrome (BSS) patient. After full megakaryocyte differentiation in culture, both hiPSC mutations showed large proplatelet tips under fluorescence microscopy and yielded fewer but larger platelets compared with those of wild-type cells. The Capillary Western analyses revealed the lower ERK1/2 activation and higher MLC2 (Myosin light chain 2) phosphorylation in megakaryocytes with mutated GPIb. Adding a mitogen-activated protein kinase (MAPK) pathway inhibitor to wild-type hiPSCs recapitulated the phenotypes of GPIb mutations and increased MLC2 phosphorylation. Notably, a ROCK inhibitor which could inhibit MLC2 phosphorylation rescued the macrothrombocytopenia phenotypes of both GPIb alterations and wild-type hiPSCs with a MA...Continue Reading

References

Oct 31, 2009·Journal of Thrombosis and Haemostasis : JTH·S SéverinA Mazharian
Dec 3, 2009·Haematologica·Silvia GianniniPaolo Gresele
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Feb 18, 2016·Journal of Thrombosis and Haemostasis : JTH·M OthmanUNKNOWN Subcommittees on von Willebrand Disease and Platelet Physiology
Jan 4, 2017·Experimental Hematology·Qiong YangQiang Jeremy Wen
Apr 16, 2017·Haematologica·Vittorio AbbonanteAlessandra Balduini
Sep 30, 2017·Platelets·Maha Othman, Jonas Emsley
Oct 31, 2017·British Journal of Haematology·Dorsaf GhalloussiVéronique Baccini
Jun 19, 2018·Platelets·Irina PleinesMarkus Bender
Jan 19, 2019·Haematologica·Loredana BuryPaolo Gresele
Jul 29, 2019·Thrombosis and Haemostasis·Ponthip MekchayPonlapat Rojnuckarin

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Citations

Nov 10, 2021·Platelets·Jaturawat PawinwongchaiPonlapat Rojnuckarin

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