Cell Adhesion and Spreading Affect Adipogenesis from Embryonic Stem Cells: The Role of Calreticulin

Szabó, Éva; Feng, Tianshu; Dziak, Ewa; Opas, Michał

doi:10.1002/stem.137

Cited by 25 publications

(24 citation statements)

References 83 publications

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“…The stress state within the cytoskeleton and cell membrane result from the complex interaction of cell junctions, cell-extracellular matrix adhesions, and the intrinsic material properties of the cell constituents, which in turn dictate the downstream response of mechanosensitive cellular elements, such as stretch-activated ion channels, growth factor receptors, and focal adhesion sites. [6][7][8] The cell mechanical modulus is altered by changing substrate stiffness by transmitting stresses from focal adhesion sites through actin filaments and myosin II-driven contraction in the cells. 9 For instance, mesenchymal stem cells can detect and differentiate in response to differences between collagen-coated gels that mimic various stiffnesses of substrata ranging in values from soft brain to stiff osteoid.…”

Section: Introductionmentioning

confidence: 99%

Elastic Properties of Induced Pluripotent Stem Cells

Hammerick

Huang

Sun

et al. 2011

Tissue Engineering Part A

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The recent technique of transducing key transcription factors into unipotent cells (fibroblasts) to generate pluripotent stem cells (induced pluripotent stem cells [iPSCs]) has significantly changed the stem cell field. These cells have great promise for many clinical applications, including that of regenerative medicine. Our findings show that iPSCs can be derived from human adipose-derived stromal cells (hASCs), a notable advancement in the clinical applicability of these cells. To investigate differences between two iPS cell lines (fibroblast-iPSC and hASC-iPSC), and also the gold standard human embryonic stem cell, we looked at cell stiffness as a possible indicator of cell differentiation-potential differences. We used atomic force microscopy as a tool to determine stem cell stiffness, and hence differences in material properties between cells. Human fibroblast and hASC stiffness was also ascertained for comparison. Interestingly, cells exhibited a noticeable difference in stiffness. From least to most stiff, the order of cell stiffness was as follows: hASC-iPSC, human embryonic stem cell, fibroblast-iPSC, fibroblasts, and, lastly, as the stiffest cell, hASC. In comparing hASC-iPSCs to their origin cell, the hASC, the reprogrammed cell is significantly less stiff, indicating that greater differentiation potentials may correlate with a lower cellular modulus. The stiffness differences are not dependent on cell culture density; hence, material differences between cells cannot be attributed solely to cell-cell constraints. The change in mechanical properties of the cells in response to reprogramming offers insight into how the cell interacts with its environment and might lend clues to how to efficiently reprogram cell populations as well as how to maintain their pluripotent state.

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Section: Introductionmentioning

confidence: 99%

Elastic Properties of Induced Pluripotent Stem Cells

Hammerick

Huang

Sun

et al. 2011

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…Soft substrata promote stem cell commitment into neurons, stiffer matrices cause cells to develop into myoblasts, whereas adhesion to rigid matrices leads to osteogenesis [10]. During adipogenesis, changes in cell spreading play an important regulatory role in the differentiation of stem cells into adipocytes [11,12]. The collective body of evidence strongly implies that decreased cell adhesiveness and spreading promotes stem cell commitment to the adipocyte lineage.…”

Section: Introductionmentioning

confidence: 99%

“…Increased CaMKII activity decreases cell adhesiveness and regulates C/EBPα expression to promote adipogenesis [17,21,22]. The ablation of calreticulin significantly increases the adipogenic potentials of mouse ES cells, while it concomitantly induces a poorly adhesive phenotype [12,17]. In addition to direct influence through the calmodulin/CaMKII pathway, calreticulin also prevents adipogenesis via focal adhesion-mediated cell adhesion [12].…”

Section: Introductionmentioning

confidence: 99%

“…The ablation of calreticulin significantly increases the adipogenic potentials of mouse ES cells, while it concomitantly induces a poorly adhesive phenotype [12,17]. In addition to direct influence through the calmodulin/CaMKII pathway, calreticulin also prevents adipogenesis via focal adhesion-mediated cell adhesion [12]. Indeed, a spread phenotype prevents adipogenesis [11,12,23,24].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to direct influence through the calmodulin/CaMKII pathway, calreticulin also prevents adipogenesis via focal adhesion-mediated cell adhesion [12]. Indeed, a spread phenotype prevents adipogenesis [11,12,23,24]. Alterations in cell adhesion lead to changes in cell shape, therefore a number of factors may elicit the proadipogenic signal.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cytoskeletal Disassembly and Cell Rounding Promotes Adipogenesis from ES Cells

Feng

Szabó

Dziak

et al. 2010

Stem Cell Rev and Rep

Self Cite

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Biomechanical signals such as cell shape and spreading play an important role in controlling stem cell commitment. Cell shape, adhesion and spreading are also affected by calreticulin, a multifunctional calcium-binding protein, which influences several cellular processes, including adipogenesis. Here we show that cytoskeletal disruption in mouse embryonic stem cells using cytochalasin D or nocodazole promotes adipogenesis. While cytochalasin D disrupts stress fibres and inhibits focal adhesion formation, nocodazole depolymerises microtubules and promotes focal adhesion formation. Furthermore, cytochalasin D increases the levels of both total and activated calcium/calmodulin-dependent protein kinase II, whereas nocodazole decreases it. Nevertheless, both treatments significantly increase the adipogenic potential of embryonic stem cells in vitro. Both cytochalasin D and nocodazole exposure caused cell rounding suggesting that it is cell shape that causes the switch towards the adipogenic programme. Calreticulin-containing embryonic stem cells, under baseline conditions, show low adipogenic potential, have low activity of signalling via calcium/calmodulin-dependent protein kinase II and display normal adhesive properties and cellular spreading in comparison to the highly adipogenic but poorly spread calreticulin-deficient ES cells. We conclude that forced cell rounding via cytoskeletal disruption overrides the effects of calreticulin, an ER chaperone, thus negatively regulating adipogenesis via focal adhesion-mediated cell spreading.

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Comparison of the proteomes of mouse Skin Derived Precursors (SKPs) and SKP‐derived fibroblasts (SFBs) by iTRAQ

Mao

Xiong

2017

J of Cellular Biochemistry

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Skin-derived precursors (SKPs) can differentiate into fibroblasts. However, little is known about the molecular mechanism of the differentiation process. Our previous study has compared the transcriptomes of mouse SKPs and SKP-derived fibroblasts (SFBs) by RNA-Seq analysis and found some genes and signal pathways that might play important roles in the transition from SKPs to SFBs. Here, to further investigate the process by which SKPs differentiate into fibroblasts, we compared the proteomes between SKPs and SFBs using iTRAQ. Our results showed that 243 differentially expressed proteins (DEPs) were identified. Among the 28 DEPs which were related to the functional group of cell differentiation, Down-regulated DEPs collagen XVIII, keratin 10, keratin 5, keratin 14, and TIFIbeta, up-regulated DEPs Thy-1, ANXA1, alpha-catenin, and calreticulin might play important roles in the transition of SKPs to fibroblasts. Further study is needed to clarify the roles of these proteins in the differentiation process of SKPs into fibroblasts, which could facilitate investigations of the detailed molecular mechanisms in the process and make it possible to take advantage of the potential therapeutic applications of SKPs in skin regeneration in the future. K E Y W O R D Sfibroblasts, iTRAQ, proteomes, skin derived precursors 1 | INTRODUCTION Skin-derived precursors (SKPs) from dermis possess the capacities of self-renewal and multipotency. 1,2 Fibroblasts are predominant cells in dermis, which play a pivotal role in maintaining the normal form and function of skin. It has been reported that SKPs can differentiate into fibroblasts. Our previous study 3 showed that SKPs developed into fibroblastlike morphology and expressed fibroblast markers fibronectin, vimentin, and collagen 7 days after being cultured in high glucose DMEM with 10% fetal bovine serum. Biernaskie et al 4,5 reported that SKPs became morphological similar to the endogenous fibroblasts and expressed fibroblast markers after transplanted into dermis. Both in vitro and in vivo experiments proved that SKPs can be induced into fibroblasts, which indicate that SKPs can be used for skin regeneration.It is important to understand the molecular process of SKPs differentiate into fibroblast for the success of cell based therapies. We previously compared the transcriptomes of SKPs and SKP-derived fibroblasts (SFBs) using RNA-Seq. 3 The results showed that nearly 2000 differentially expressed genes (DEGs) were identified. The different expression levels of proteins play an important role in cell growth, environment stimulation reaction, and stem cell differentiation as well.

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Cell Adhesion and Spreading Affect Adipogenesis from Embryonic Stem Cells: The Role of Calreticulin

Cited by 25 publications

References 83 publications

Elastic Properties of Induced Pluripotent Stem Cells

Elastic Properties of Induced Pluripotent Stem Cells

Cytoskeletal Disassembly and Cell Rounding Promotes Adipogenesis from ES Cells

Comparison of the proteomes of mouse Skin Derived Precursors (SKPs) and SKP‐derived fibroblasts (SFBs) by iTRAQ

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