Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide

BMC Cell Biology

Research Article

Olesja Hazenbiller¹  Roman J. Krawetz²  Neil A. Duncan³ 

[1] McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada;McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada;Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive N.W, T2N 4N1, Calgary, AB, Canada;McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada;Department of Civil Engineering Schulich School of Engineering, University of Calgary, Calgary, Canada;

关键词: Embryonic stem cell;    Collagen type I;    Cyclic RGD peptide;    Confined compression;    Integrins;    Mechano-transduction;   

DOI  :  10.1186/s12860-017-0148-6

 received in 2017-01-27, accepted in 2017-11-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundSelf-renewal and differentiation of embryonic stem cells (ESCs) is directed by biological and/or physical cues that regulate multiple signaling cascades. We have previously shown that mESCs seeded in a type I collagen matrix demonstrate a loss of pluripotent marker expression and differentiate towards an osteogenic lineage. In this study, we examined if this effect was mediated in part through Arginylglycylaspartic acid (RGD) dependent integrin activity and/or mechano-transduction.ResultsThe results from this study suggest that mESC interaction with the local microenvironment through RGD dependent integrins play a role in the regulation of mESC core transcription factors (TF), Oct-4, Sox 2 and Nanog. Disruption of this interaction with a cyclic RGD peptide (cRGDfC) was sufficient to mimic the effect of a mechanical stimulus in terms of pluripotent gene expression, specifically, we observed that supplementation with cRGDfC, or mechanical stimulus, significantly influenced mESC pluripotency by down-regulating core transcription factors. Moreover, our results indicated that the presence of the cRGDfC peptide inhibited integrin expression and up-regulated early lineage markers (mesoderm and ectoderm) in a Leukemia inhibitory factor (LIF) dependent manner. When cRGDfC treated mESCs were injected in Severe combined immunodeficiency (SCID) mice, no tissue growth and/or teratoma formation was observed, suggesting that the process of mESC tumor formation in vivo is potentially dependent on integrin interaction.ConclusionsOverall, the disruption of cell-integrin interaction via cRGDfC peptide can mimic the effect of mechanical stimulation on mESC pluripotency gene expression and also inhibit the tumorigenic potential of mESCs in vivo.

【 授权许可】

CC BY   
© The Author(s). 2017