Open AccessExtracellular vesicles synchronize cellular phenotypes of differentiating cells
Author(s) -
Minakawa Tomohiro,
Matoba Tetsuya,
Ishidate Fumiyoshi,
Fujiwara Takahiro K.,
Takehana Sho,
Tabata Yasuhiko,
Yamashita Jun K.
Publication year - 2021
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12147
Subject(s) - microbiology and biotechnology , mesoderm , embryonic stem cell , phenotype , cellular differentiation , cell fate determination , biology , extracellular vesicles , hek 293 cells , vesicle , cell type , cell , cell culture , gene , genetics , transcription factor , membrane
During embryonic development, cells differentiate in a coordinated manner, aligning their fate decisions and differentiation stages with those of surrounding cells. However, little is known about the mechanisms that regulate this synchrony. Here we show that cells in close proximity synchronize their differentiation stages and cellular phenotypes with each other via extracellular vesicle (EV)‐mediated cellular communication. We previously established a mouse embryonic stem cell (ESC) line harbouring an inducible constitutively active protein kinase A (CA‐PKA) gene and found that the ESCs rapidly differentiated into mesoderm after PKA activation. In the present study, we performed a co‐culture of Control‐ESCs and PKA‐ESCs, finding that both ESC types rapidly differentiated in synchrony even when PKA was activated only in PKA‐ESCs, a phenomenon we named ‘Phenotypic Synchrony of Cells (PSyC)’. We further demonstrated PSyC was mediated by EVs containing miR‐132. PKA‐ESC‐derived EVs and miR‐132‐containing artificial nano‐vesicles similarly enhanced mesoderm and cardiomyocyte differentiation in ESCs and ex vivo embryos, respectively. PSyC is a new form of cell‐cell communication mediated by the EV regulation of neighbouring cells and could be broadly involved in tissue development and homeostasis.