Evidence of Extracellular Vesicles Biogenesis and Release in Mouse Embryonic Stem Cells

Author(s)

Cruz, Lilian ; Arevalo Romero, Jenny Andrea ; Prado, Mariana Brandao ; Santos, Tiago G. ; Lopes, Marilene Hohmuth

• Document type: Journal article
• Source: STEM CELL REVIEWS AND REPORTS; v. 14, n. 2, p. 15-pg., 2018-04-01.

Abstract

Extracellular vesicles (EVs) released by mouse embryonic stem cells (mESCs) are considered a source of bioactive molecules that modulate their microenvironment by acting on intercellular communication. Either intracellular endosomal machinery or their derived EVs have been considered a relevant system of signal circuits processing. Herein, we show that these features are found in mESCs. Ultrastructural analysis revealed structures and organelles of the endosomal system such as coated pits and endocytosis-related vesicles, prominent rough endoplasmic reticulum and Golgi apparatus, and multivesicular bodies (MVBs) containing either few or many intraluminal vesicles (ILVs) that could be released as exosomes to extracellular milieu. Besides, budding vesicles shed from the plasma membrane to the extracellular space is suggestive of microvesicle biogenesis in mESCs. mESCs and mouse blastocyst express specific markers of the Endosomal Sorting Complex Required for Transport (ESCRT) system. Ultrastructural analysis and Nanoparticle Tracking Analysis (NTA) of isolated EVs revealed a heterogeneous population of exosomes and microvesicles released by mESCs. These vesicles contain Wnt10b and the Notch ligand Delta-like 4 (DLL4) and also the co-chaperone stress inducible protein 1 (STI1) and its partner Hsp90. Wnt10b and Dll4 colocalize with EVs biogenesis markers in mESCs. Overall, the present study supports the function of the mESCs endocytic network and their EVs as players in stem cell biology. (AU)

• FAPESP's process: 11/13906-2 - Contribution of the co-chaperone STI1 in mouse development: embryonic stem cell as approach
• Grantee: Marilene Hohmuth Lopes
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/22078-1 - Profile of extracellular vesicles miRNA in the neuronal differentiation of murine embryonic stem cells
• Grantee: Lilian Cruz
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 14/17385-5 - Impact of the depletion of the co-chaperone STI1 in the control of pluripotency, proliferation and differentiation of murine embryonic stem cells
• Grantee: Jenny Andrea Arévalo Romero
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)