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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2018; 10(9): 119-133
Published online Sep 26, 2018. doi: 10.4252/wjsc.v10.i9.119
Regulatory role of sphingosine kinase and sphingosine-1-phosphate receptor signaling in progenitor/stem cells
Mei Li Ng, Nagendra S Yarla, Mario Menschikowski, Olga A Sukocheva
Mei Li Ng, Centenary Institute of Cancer Medicine and Cell Biology, Sydney NSW 2050, Australia
Nagendra S Yarla, Department of Biochemistry and Bioinformatics, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Andhra Pradesh, India
Mario Menschikowski, Institute of Clinical Chemistry and Laboratory Medicine, Carl Gustav Carus University Hospital, Technical University of Dresden, Dresden D-01307, Germany
Olga A Sukocheva, College of Nursing and Health Sciences, Flinders University of South Australia, Bedford Park SA 5042, Australia
Author contributions: Sukocheva OA and Menschikowski M conceptualized the original idea, designed the review concept, and wrote introductory and conclusive parts of the study; Ng ML and Yarla NS collected the required data and wrote different chapters of the manuscript; Sukocheva OA and Ng ML drew the figures; all authors read and approved the final manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Olga A Sukocheva, MSc, PhD, Lecturer, College of Nursing and Health Sciences, Flinders University of South Australia, Flinders Drive, Bedford Park SA 5042, Australia. olga.sukocheva@flinders.edu.au
Telephone: +61-8-82013648 Fax: +61-8-82017500
Received: April 27, 2018
Peer-review started: April 27, 2018
First decision: June 6, 2018
Revised: July 27, 2018
Accepted: August 5, 2018
Article in press: August 5, 2018
Published online: September 26, 2018
Processing time: 152 Days and 1 Hours
Abstract

Balanced sphingolipid signaling is important for the maintenance of homeostasis. Sphingolipids were demonstrated to function as structural components, second messengers, and regulators of cell growth and survival in normal and disease-affected tissues. Particularly, sphingosine kinase 1 (SphK1) and its product sphingosine-1-phosphate (S1P) operate as mediators and facilitators of proliferation-linked signaling. Unlimited proliferation (self-renewal) within the regulated environment is a hallmark of progenitor/stem cells that was recently associated with the S1P signaling network in vasculature, nervous, muscular, and immune systems. S1P was shown to regulate progenitor-related characteristics in normal and cancer stem cells (CSCs) via G-protein coupled receptors S1Pn (n = 1 to 5). The SphK/S1P axis is crucially involved in the regulation of embryonic development of vasculature and the nervous system, hematopoietic stem cell migration, regeneration of skeletal muscle, and development of multiple sclerosis. The ratio of the S1P receptor expression, localization, and specific S1P receptor-activated downstream effectors influenced the rate of self-renewal and should be further explored as regeneration-related targets. Considering malignant transformation, it is essential to control the level of self-renewal capacity. Proliferation of the progenitor cell should be synchronized with differentiation to provide healthy lifelong function of blood, immune systems, and replacement of damaged or dead cells. The differentiation-related role of SphK/S1P remains poorly assessed. A few pioneering investigations explored pharmacological tools that target sphingolipid signaling and can potentially confine and direct self-renewal towards normal differentiation. Further investigation is required to test the role of the SphK/S1P axis in regulation of self-renewal and differentiation.

Keywords: Sphingosine-1-phosphate; Sphingolipids; Embryonic stem cells; Mesenchymal stem cells; Bone marrow hematopoietic stem cells; Sphingosine kinase; Progenitor

Core tip: The aim of this study is to review the role of sphingosine kinase, sphingosine-1-phosphate (S1P), and its receptors in the regulation of stem/progenitor cell function. Our analysis indicates that S1P receptor expression, localization, and specific downstream effectors influence the rate of self-renewal and differentiation of myogenic, hematopoietic, endothelial, neural, and cancer progenitor cells.