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CD34(+) HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin

Exosomes are tiny vesicles released by cells that carry communications to local and distant locations. Emerging research has revealed the role played by integrins found on the surface of exosomes in delivering information once they reach their destination. But until now, little has been known on the...

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Autores principales: Isaioglou, Ioannis, Aldehaiman, Mansour M., Li, Yanyan, Lahcen, Abdellatif Ait, Rauf, Sakandar, Al-Amoodi, Asma S., Habiba, Umme, Alghamdi, Abdullah, Nozue, Shuho, Habuchi, Satoshi, Salama, Khaled N., Merzaban, Jasmeen S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166801/
https://www.ncbi.nlm.nih.gov/pubmed/37181754
http://dx.doi.org/10.3389/fcell.2023.1149912
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author Isaioglou, Ioannis
Aldehaiman, Mansour M.
Li, Yanyan
Lahcen, Abdellatif Ait
Rauf, Sakandar
Al-Amoodi, Asma S.
Habiba, Umme
Alghamdi, Abdullah
Nozue, Shuho
Habuchi, Satoshi
Salama, Khaled N.
Merzaban, Jasmeen S.
author_facet Isaioglou, Ioannis
Aldehaiman, Mansour M.
Li, Yanyan
Lahcen, Abdellatif Ait
Rauf, Sakandar
Al-Amoodi, Asma S.
Habiba, Umme
Alghamdi, Abdullah
Nozue, Shuho
Habuchi, Satoshi
Salama, Khaled N.
Merzaban, Jasmeen S.
author_sort Isaioglou, Ioannis
collection PubMed
description Exosomes are tiny vesicles released by cells that carry communications to local and distant locations. Emerging research has revealed the role played by integrins found on the surface of exosomes in delivering information once they reach their destination. But until now, little has been known on the initial upstream steps of the migration process. Using biochemical and imaging approaches, we show here that exosomes isolated from both leukemic and healthy hematopoietic stem/progenitor cells can navigate their way from the cell of origin due to the presence of sialyl Lewis X modifications surface glycoproteins. This, in turn, allows binding to E-selectin at distant sites so the exosomes can deliver their messages. We show that when leukemic exosomes were injected into NSG mice, they traveled to the spleen and spine, sites typical of leukemic cell engraftment. This process, however, was inhibited in mice pre-treated with blocking E-selectin antibodies. Significantly, our proteomic analysis found that among the proteins contained within exosomes are signaling proteins, suggesting that exosomes are trying to deliver active cues to recipient cells that potentially alter their physiology. Intriguingly, the work outlined here also suggests that protein cargo can dynamically change upon exosome binding to receptors such as E-selectin, which thereby could alter the impact it has to regulate the physiology of the recipient cells. Furthermore, as an example of how miRNAs contained in exosomes can influence RNA expression in recipient cells, our analysis showed that miRNAs found in KG1a-derived exosomes target tumor suppressing proteins such as PTEN.
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spelling pubmed-101668012023-05-10 CD34(+) HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin Isaioglou, Ioannis Aldehaiman, Mansour M. Li, Yanyan Lahcen, Abdellatif Ait Rauf, Sakandar Al-Amoodi, Asma S. Habiba, Umme Alghamdi, Abdullah Nozue, Shuho Habuchi, Satoshi Salama, Khaled N. Merzaban, Jasmeen S. Front Cell Dev Biol Cell and Developmental Biology Exosomes are tiny vesicles released by cells that carry communications to local and distant locations. Emerging research has revealed the role played by integrins found on the surface of exosomes in delivering information once they reach their destination. But until now, little has been known on the initial upstream steps of the migration process. Using biochemical and imaging approaches, we show here that exosomes isolated from both leukemic and healthy hematopoietic stem/progenitor cells can navigate their way from the cell of origin due to the presence of sialyl Lewis X modifications surface glycoproteins. This, in turn, allows binding to E-selectin at distant sites so the exosomes can deliver their messages. We show that when leukemic exosomes were injected into NSG mice, they traveled to the spleen and spine, sites typical of leukemic cell engraftment. This process, however, was inhibited in mice pre-treated with blocking E-selectin antibodies. Significantly, our proteomic analysis found that among the proteins contained within exosomes are signaling proteins, suggesting that exosomes are trying to deliver active cues to recipient cells that potentially alter their physiology. Intriguingly, the work outlined here also suggests that protein cargo can dynamically change upon exosome binding to receptors such as E-selectin, which thereby could alter the impact it has to regulate the physiology of the recipient cells. Furthermore, as an example of how miRNAs contained in exosomes can influence RNA expression in recipient cells, our analysis showed that miRNAs found in KG1a-derived exosomes target tumor suppressing proteins such as PTEN. Frontiers Media S.A. 2023-04-25 /pmc/articles/PMC10166801/ /pubmed/37181754 http://dx.doi.org/10.3389/fcell.2023.1149912 Text en Copyright © 2023 Isaioglou, Aldehaiman, Li, Lahcen, Rauf, Al-Amoodi, Habiba, Alghamdi, Nozue, Habuchi, Salama and Merzaban. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Isaioglou, Ioannis
Aldehaiman, Mansour M.
Li, Yanyan
Lahcen, Abdellatif Ait
Rauf, Sakandar
Al-Amoodi, Asma S.
Habiba, Umme
Alghamdi, Abdullah
Nozue, Shuho
Habuchi, Satoshi
Salama, Khaled N.
Merzaban, Jasmeen S.
CD34(+) HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin
title CD34(+) HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin
title_full CD34(+) HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin
title_fullStr CD34(+) HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin
title_full_unstemmed CD34(+) HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin
title_short CD34(+) HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin
title_sort cd34(+) hspcs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor e-selectin
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166801/
https://www.ncbi.nlm.nih.gov/pubmed/37181754
http://dx.doi.org/10.3389/fcell.2023.1149912
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