Abstract

Thrombopoietin (TPO), a glycoprotein hormone produced predominantly in the liver, plays important roles in the hematopoietic stem cell (HSC) niche, and is essential for megakaryopoiesis and platelet generation. Long‐standing understanding proposes that TPO is constitutively produced by hepatocytes, and levels are fine‐tuned through platelet and megakaryocyte internalization/degradation via the c‐Mpl receptor. However, in immune thrombocytopenia (ITP) and several other diseases, TPO levels are inconsistent with this theory. Recent studies showed that platelets, besides their TPO clearance, can induce TPO production in the liver. Our group also accidentally discovered that platelet glycoprotein (GP) Ibα is required for platelet‐mediated TPO generation, which is underscored in both GPIbα−/− mice and patients with Bernard‐Soulier syndrome. This review will introduce platelet versatilities and several new findings in hemostasis and platelet consumption but focus on its roles in TPO regulation. The implications of these new discoveries in hematopoiesis and the HSC niche, particularly in ITP, will be discussed.

Details

Title
GPIbα is the driving force of hepatic thrombopoietin generation
Author
Karakas, Danielle 1 ; Xu, Miao 2 ; Ni, Heyu 3   VIAFID ORCID Logo 

1  Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Toronto Platelet Immunobiology Group, Toronto, ON, Canada; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, Canada 
2  Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China 
3  Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Toronto Platelet Immunobiology Group, Toronto, ON, Canada; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, Canada; Canadian Blood Services Centre for Innovation, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada 
Section
STATE OF THE ART ISTH 2020
Publication year
2021
Publication date
May 2021
Publisher
Elsevier Limited
e-ISSN
24750379
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1002/rth2.12506
ProQuest document ID
2534508156
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.