The self-renewal of mouse embryonic stem cells is regulated by cell–substratum adhesion and cell spreading

Murray, Patricia; Prewitz, Marina; Hopp, Isabel; Wells, Nicola; Zhang, Haifei; Cooper, Andrew I.; Parry, Kristina L.; Short, Robert D.; Antoine, Daniel J.; Edgar, David

doi:10.1016/j.biocel.2013.07.001

Cited by 36 publications

(49 citation statements)

References 41 publications

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“…The discrepancy between previous reports and our current study may result from the fact that most of the total population of tumor cells are probably differentiated tumor cells in those previous reports whereas only undifferentiated TRCs are analyzed in our present study [10]. Our results are consistent with the previous findings that the reduction in FAK activity promotes growth of stem cells [29] while the elevation in FAK activity facilitates their differentiation [30]. These findings may explain why FAK inhibition may not block tumorigenic cell proliferation as the current strategy in clinical trials of the candidate drugs to inhibit FAK does not work [31].…”

Section: Discussionsupporting

confidence: 71%

Soft matrices downregulate FAK activity to promote growth of tumor-repopulating cells

Tan

Wood

Jia

et al. 2017

Biochemical and Biophysical Research Communications

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Tumor-repopulating cells are a tumorigenic sub-population of cancer cells that drives tumorigenesis. We have recently reported that soft fibrin matrices maintain tumor-repopulating cell growth by promoting histone 3 lysine 9 (H3K9) demethylation and Sox2 expression and that Cdc42 expression influences H3K9 methylation. However, the underlying mechanisms of how soft matrices induce H3K9 demethylation remain elusive. Here we find that tumor-repopulating cells exhibit lower focal adhesion kinase (FAK) and H3K9 methylation levels in soft fibrin matrices than control melanoma cells on 2D rigid substrates. Silencing FAK in control melanoma cells decreases H3K9 methylation, whereas overexpressing FAK in tumor-repopulating cells enhances H3K9 methylation. Overexpressing Cdc42 or RhoA in the presence of FAK knockdown restores H3K9 methylation levels. Importantly, silencing FAK, Cdc42, or RhoA promotes Sox2 expression and proliferation of control melanoma cells in stiff fibrin matrices, whereas overexpressing each gene suppresses Sox2 expression and reduces growth of TRCs in soft but not in stiff fibrin matrices. Our findings suggest that low FAK mediated by soft fibrin matrices downregulates H3K9 methylation through reduction of Cdc42 and RhoA and promotes growth of tumor-repopulating cells.

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Section: Discussionsupporting

confidence: 71%

Soft matrices downregulate FAK activity to promote growth of tumor-repopulating cells

Tan

Wood

Jia

et al. 2017

Biochemical and Biophysical Research Communications

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“…(E)]. Although the PLGA was not harmful to the cells it was also not really promoting them, as is obvious from the data shown for polyethersulfone (PES) treated with collagen scaffolds . It was described that mESCs cultivated on PES treated with collagen (PES‐COL) scaffolds presented a significantly higher proliferation rate than the PES or gelatin after 96 h .…”

Section: Discussionmentioning

confidence: 98%

Effect of feeder free poly(lactide‐co‐glycolide) scaffolds on morphology, proliferation, and pluripotency of mouse embryonic stem cells

Galuppo

Chagastelles

Gamba

et al. 2016

J Biomedical Materials Res

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The aim of the study has been to evaluate the morphology, proliferation, and pluripotency maintenance of mouse embryonic stem cells (mESCs) cultivated on poly(lactic-co-glycolic acid) scaffolds. The scaffolds were hydrolyzed with NaOH (treated) and nonhydrolyzed (untreated). Morphological and mechanical characterization of the scaffolds was performed. mESC were evaluated for cell viability, cytotoxicity, expression of pluripotency markers, colony morphology, and overall distribution. The treatment generated a reduction in the hydrophobic characteristics of the scaffolds, leading to a higher wettability compared to the untreated group. The viability, cytotoxicity, number of colonies, and the thickness of the cell layer presented similar results between the scaffold groups. The viability test showed that it was possible to cultivate the mESCs on the scaffolds. The cytotoxicity analysis showed that the PLGA scaffolds were not harmful for the cells. The cells maintained the expression of the pluripotency markers Oct4 and Sox2. The number of colonies and the thickness of the cell layer on the scaffold showed that they were not able to colonize the entire volume of the scaffolds. The area occupied by the mESCs was the same between the treated and untreated groups after 14 days in culture. It is possible to conclude that both conditions are equally suitable for maintaining mESC culture. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 424-432, 2017.

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“…Cytoskeleton rearrangement and the Rho-ROCK pathway are critical for both MSC differentiation and ESC self-renewal6566. Here we showed that the Rho-Rock-actin/myosin pathway is important for both cell fusion and entosis in ESCs.…”

Section: Discussionmentioning

confidence: 77%

Mesenchymal stem cells generate distinct functional hybrids in vitro via cell fusion or entosis

Sottile

Aulicino

Theka

et al. 2016

Sci Rep

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Homotypic and heterotypic cell-to-cell fusion are key processes during development and tissue regeneration. Nevertheless, aberrant cell fusion can contribute to tumour initiation and metastasis. Additionally, a form of cell-in-cell structure called entosis has been observed in several human tumours. Here we investigate cell-to-cell interaction between mouse mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs). MSCs represent an important source of adult stem cells since they have great potential for regenerative medicine, even though they are also involved in cancer progression. We report that MSCs can either fuse forming heterokaryons, or be invaded by ESCs through entosis. While entosis-derived hybrids never share their genomes and induce degradation of the target cell, fusion-derived hybrids can convert into synkaryons. Importantly we show that hetero-to-synkaryon transition occurs through cell division and not by nuclear membrane fusion. Additionally, we also observe that the ROCK-actin/myosin pathway is required for both fusion and entosis in ESCs but only for entosis in MSCs. Overall, we show that MSCs can undergo fusion or entosis in culture by generating distinct functional cellular entities. These two processes are profoundly different and their outcomes should be considered given the beneficial or possible detrimental effects of MSC-based therapeutic applications.

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The self-renewal of mouse embryonic stem cells is regulated by cell–substratum adhesion and cell spreading

Cited by 36 publications

References 41 publications

Soft matrices downregulate FAK activity to promote growth of tumor-repopulating cells

Soft matrices downregulate FAK activity to promote growth of tumor-repopulating cells

Effect of feeder free poly(lactide‐co‐glycolide) scaffolds on morphology, proliferation, and pluripotency of mouse embryonic stem cells

Mesenchymal stem cells generate distinct functional hybrids in vitro via cell fusion or entosis

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