Inhibition of Tropomyosin Receptor Kinase A Signaling Negatively Regulates Megakaryopoiesis and induces Thrombopoiesis

Scientific Reports
Ayse KizilyerSanjay B Maggirwar

Abstract

Neurotrophin signaling modulates the differentiation and function of mature blood cells. The expression of neurotrophin receptors and ligands by hematopoietic and stromal cells of the bone marrow indicates that neurotrophins have the potential to regulate hematopoietic cell fate decisions. This study investigates the role of neurotrophins and Tropomyosin receptor kinases (Trk) in the development of megakaryocytes (MKs) and their progeny cells, platelets. Results indicate that primary human MKs and MK cells lines, DAMI, Meg-01 and MO7e express TrkA, the primary receptor for Nerve Growth Factor (NGF) signaling. Activation of TrkA by NGF enhances the expansion of human MK progenitors (MKPs) and, to some extent, MKs. Whereas, inhibition of TrkA receptor by K252a leads to a 50% reduction in the number of both MKPs and MKs and is associated with a 3-fold increase in the production of platelets. In order to further confirm the role of TrkA signaling in platelet production, TrkA deficient DAMI cells were generated using CRISPR-Cas9 technology. Comparative analysis of wild-type and TrkA-deficient Dami cells revealed that loss of TrkA signaling induced apoptosis of MKs and increased platelet production. Overall, these findings support a ...Continue Reading

References

Dec 1, 1992·Journal of Neurochemistry·B Knüsel, F Hefti
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·H MatsudaJ A Denburg
Jun 1, 1995·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·U Otten, R A Gadient
Feb 4, 1998·Archives of Biochemistry and Biophysics·T S AngelesC A Dionne
Feb 23, 1999·The American Journal of Pathology·E LabouyrieJ P Merlio
Jun 26, 1999·Microscopy Research and Technique·L AloeF Properzi
Sep 1, 2001·Cellular and Molecular Life Sciences : CMLS·H Sariola
Jan 5, 2002·American Journal of Hematology·H KawasakiY Kobayashi
Feb 28, 2002·The Journal of Biological Chemistry·Natalie O KarpinichJohn L Farber
Mar 7, 2003·Journal of Neuroimmunology·Luisa Bracci-LaudieroLuigi Aloe
Apr 5, 2003·Annual Review of Biochemistry·Eric J Huang, Louis F Reichardt
Aug 2, 2003·Journal of Anatomy·José A VegaAntonino Germanà
Mar 19, 2004·The New England Journal of Medicine·Andrew I Schafer
Oct 2, 2004·Development·Vincenzo CoppolaLino Tessarollo
Feb 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·James C MulloyStephen D Nimer
Mar 22, 2005·British Journal of Pharmacology·Michael P Gordge
Nov 15, 2005·The Journal of Pharmacology and Experimental Therapeutics·Judy J WatsonDavid Dawbarn
Dec 27, 2005·Trends in Pharmacological Sciences·Franz F HeftiAlun M Davies
Jul 22, 2006·Biochemical Society Transactions·D DawbarnS J Allen
Aug 31, 2006·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Louis F Reichardt
Nov 10, 2007·Cell Death and Differentiation·A CaporaliC Emanueli
Nov 21, 2007·Hematology·Alessandro M Vannucchi, Tiziano Barbui
Dec 21, 2007·Critical Reviews in Oncology/hematology·Cuiling ZhengMin Lu
Jan 15, 2008·Clinical and Experimental Immunology·B SamahG Gras
May 31, 2008·British Journal of Haematology·Eldad Hod, Joseph Schwartz
Aug 30, 2008·Blood·Jamie J O'BrienRichard P Phipps
Jan 8, 2009·Physiological Reviews·Andrea Caporali, Costanza Emanueli
Aug 21, 2009·Journal of Thrombosis and Haemostasis : JTH·S S SmythUNKNOWN 2009 Platelet Colloquium Participants
Sep 12, 2009·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Jaisy Mathai
Dec 17, 2009·Hematology·Radek C Skoda

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Citations

Aug 21, 2020·Journal of the American Heart Association·Emily A WeberSanjay B Maggirwar

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Methods Mentioned

BETA
flow cytometry
electrophoresis
Infrared Imaging
PCR
fluorescence-activated cell sorting
gene knockout

Software Mentioned

TreeStar
Image Studio Lite
FlowJo
Graphpad Prism

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