Embryonic Stem Cell-Derived Extracellular Vesicles Maintain ESC Stemness by Activating FAK

Hur, Yun Ha; Shi, Feng; Wilson, Kristin; Cerione, Richard A.; Antonyak, Marc A.

doi:10.1016/j.devcel.2020.11.017

Cited by 50 publications

(40 citation statements)

References 61 publications

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“…Altogether, our data highlight the unique role of a specific ECM component of the niche, namely fibronectin, in HFSC activation. In accordance with recent data on maintenance of ES cells pluripotency by fibronectin 24 , our results demonstrate that it plays a crucial role in adult stem cells maintenance too. On a more conceptual point of view, we show that ECM specific anchoring signal via fibronectin tunes HFSC fate and regenerative power of this population.…”

Section: Mainsupporting

confidence: 93%

Fibronectin meshwork controls epithelial stem cell fate

Estrach

Tosello

Tissot

et al. 2021

Preprint

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Adult stem cell fate is tightly balanced by the local microenvironment called niche and sustain tissue regeneration. How niche signals are integrated and regulate regeneration remains largely unexplored. The extracellular matrix and integrin ligand fibronectin is a crucial and well-characterized wound healing actor that has never been involved in skin regeneration. Here, we show that fibronectin displays a highly specific enrichment in hair follicle stem cells (HFSC) at the onset of regeneration. Conditional deletion of fibronectin in HFSC compartment (Lrig1, K19) leads to hair regeneration blockade, impaired stem cell location and fate. Dermal injection of exogenous fibronectin rescues these phenotypes. To elucidate molecular mechanism underlying fibronectin function, we used conditional deletion models of SLC3A2, the main integrin coreceptor. We show that, via its role in integrin-dependent assembly of fibronectin matrix, SLC3A2 acts as molecular relay of niche signals. Thus, fibronectinintegrin-SLC3A2 cascade finely tunes HFSC fate and tissue regenerative power.

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Section: Mainsupporting

confidence: 93%

Fibronectin meshwork controls epithelial stem cell fate

Estrach

Tosello

Tissot

et al. 2021

Preprint

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“…In fibrosarcoma cells, fibronectin bound to a5b1 integrin on exosomes was shown to directly promote adhesion formation and cell speed (Sung et al, 2015). Fibronectin and laminins can also be carried by large EVs where, in association with the ECM crosslinking molecule tissue transglutaminase 2 (TG2), they have been shown to enhance focal adhesion kinase (FAK) activation and trophoblast cell migration (Antonyak et al, 2011;Desrochers et al, 2016;Hur et al, 2021). As a variety of ECM components have been identified to be associated with EVs (Jimenez et al, 2019;Rilla et al, 2019;Yeung et al, 2020), an interesting future direction will be to determine whether the presentation of ECM molecules by EVs is a general mechanism that promotes adhesion formation by diverse types of migrating cells.…”

Section: Evs In Cell Adhesionmentioning

confidence: 99%

Extracellular vesicles: Critical players during cell migration

2021

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Cell migration is essential for the development and maintenance of multicellular organisms, contributing to embryogenesis, wound healing, immune response, and other critical processes. It is also involved in the pathogenesis of many diseases, including immune deficiency disorders and cancer metastasis. Recently, extracellular vesicles (EVs) have been shown to play important roles in cell migration. Here, we review recent studies describing the functions of EVs in multiple aspects of cell motility, including directional sensing, cell adhesion, extracellular matrix (ECM) degradation, and leader-follower behavior. We also discuss the role of EVs in migration during development and disease and the utility of imaging tools for studying the role of EVs in cell migration.

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“…For example, it has been reported that Cav1 KO adipocytes receive Cav1 mRNA from surrounding endothelial cells via EVs, allowing the KO cells to produce Cav1 protein (Crewe et al., 2018 ). Another report suggested the involvement of EVs in homeostasis, in which ESC‐derived EVs maintain the stem cell properties of ESCs even under differentiation culture conditions (Hur et al., 2021 ). Accordingly, PSyC with different conditions and environments should be investigated.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles synchronize cellular phenotypes of differentiating cells

Minakawa

Matoba

Ishidate

et al. 2021

J of Extracellular Vesicle

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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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Embryonic Stem Cell-Derived Extracellular Vesicles Maintain ESC Stemness by Activating FAK

Cited by 50 publications

References 61 publications

Fibronectin meshwork controls epithelial stem cell fate

Fibronectin meshwork controls epithelial stem cell fate

Extracellular vesicles: Critical players during cell migration

Extracellular vesicles synchronize cellular phenotypes of differentiating cells

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