TY - JOUR
T1 - Extracellular vesicles synchronize cellular phenotypes of differentiating cells
AU - Minakawa, Tomohiro
AU - Matoba, Tetsuya
AU - Ishidate, Fumiyoshi
AU - Fujiwara, Takahiro K.
AU - Takehana, Sho
AU - Tabata, Yasuhiko
AU - Yamashita, Jun K.
N1 - Funding Information:
We thank Dr. T. Matsunaga and T. Hoshino for technical suggestions; Dr. P. Karagiannis for critical reading of the manuscript; Dr. A. Watanabe, Dr. M. Nakamura and N. Amano for analysing the RNA‐seq data; Dr. Takumi Era for providing the EStTA5‐4 cell line, Dr. Feng Zhang for providing the pX330 plasmid and Dr. Knut Woltjen for providing the piggyBac vector and transposon vector; Dr. I. Baba, Kozue Nakamura, Kae Nakamura, Y. Kaji and N. Yasuhara for technical assistance; and Dr. M. Kengaku and ZEISS‐iCeMS Innovation Core at the iCeMS Analysis Centre, Kyoto University, for supporting the imaging analysis. This work was supported by JST CREST Grant Number JPMJCR17H5, Japan.
Publisher Copyright:
© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
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U2 - 10.1002/jev2.12147
DO - 10.1002/jev2.12147
M3 - Article
C2 - 34533283
AN - SCOPUS:85115195200
VL - 10
JO - Journal of Extracellular Vesicles
JF - Journal of Extracellular Vesicles
SN - 2001-3078
IS - 11
M1 - e12147
ER -