eCommons

 

EXTRACELLULAR VESICLES IN STEM CELL BIOLOGY

Other Titles

Author(s)

Abstract

Pluripotent stem cells reside transiently in the epiblast of blastocyst-stage embryos, until the proper time when they receive signals to differentiate into the germ layers that will give rise to the entire organism. However, the mechanisms that underlie the regulation of stem cell fate in the developing embryo, particularly how they maintain pluripotency, remain poorly understood. Here we show that embryonic stem cells (ESCs), the in vitro equivalents of stem cell populations within the epiblast, form and release extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, to help maintain their stemness. Treating ESCs cultured under differentiation-inducing conditions with MVs and/or exosomes isolated from pluripotent ESCs blocked their differentiation and preserved stem cell characteristics including the ability to generate chimeric animals. Such effects were determined to be dependent on the extracellular matrix protein fibronectin associated with the vesicles, and its ability to bind to integrins and activate focal adhesion kinase (FAK) in recipient cells. These findings raise the exciting possibility that EVs might serve as a mechanism that helps stem cells within the blastocyst to maintain their pluripotent state.In addition to the roles that ESC-derived EVs potentially play in the physiological setting, we made interesting discoveries showing that they also can dramatically impact the behavior of differentiated cells by causing them to behave like stem cells, and even possibly induce pluripotency. The treatment of mouse embryonic fibroblasts (MEFs), a type of somatic cell, with MVs and exosomes produced by ESCs protected the cells from serum starvation-induced cell death and delayed senescence. Moreover, the EV-treated MEFs were also found to acquire the phenotypes of stem cells, such as the ability to form spheres, exhibit alkaline phosphatase activity, and express core stemness proteins Oct3/4 and Nanog. The EVs from ESCs strongly activated the cell survival and growth-promoting protein AKT in MEFs, and when EV-mediated AKT activation was inhibited, the MEFs no longer showed stem cell-like characteristics. Collectively, these findings shed light on how a unique form of intercellular communication can have important consequences in early development, as well as can potentially be used for regenerative medicine applications.

Journal / Series

Volume & Issue

Description

169 pages

Sponsorship

Date Issued

2021-08

Publisher

Keywords

Embryonic stem cell; Exosomes; Extracellular vesicles; Microvesicles; Pluripotent stem cell; Pluriptoency

Location

Effective Date

Expiration Date

Sector

Employer

Union

Union Local

NAICS

Number of Workers

Committee Chair

Cerione, Richard A.

Committee Co-Chair

Committee Member

Kurpios, Natasza
Linder, Maurine E.
Sondermann, Holger

Degree Discipline

Biomedical and Biological Sciences

Degree Name

Ph. D., Biomedical and Biological Sciences

Degree Level

Doctor of Philosophy

Related Version

Related DOI

Related To

Related Part

Based on Related Item

Has Other Format(s)

Part of Related Item

Related To

Related Publication(s)

Link(s) to Related Publication(s)

References

Link(s) to Reference(s)

Previously Published As

Government Document

ISBN

ISMN

ISSN

Other Identifiers

Rights

Rights URI

Types

dissertation or thesis

Accessibility Feature

Accessibility Hazard

Accessibility Summary

Link(s) to Catalog Record