Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide
Abstract Background Self-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...
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doaj-d8cb96452852466f84493a20d6dabb332020-11-24T21:32:34ZengBMCBMC Cell Biology1471-21212017-11-0118111510.1186/s12860-017-0148-6Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptideOlesja Hazenbiller0Neil A. Duncan1Roman J. Krawetz2McCaig Institute for Bone and Joint Health, University of CalgaryMcCaig Institute for Bone and Joint Health, University of CalgaryMcCaig Institute for Bone and Joint Health, University of CalgaryAbstract Background Self-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. Results The 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. Conclusions Overall, 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.http://link.springer.com/article/10.1186/s12860-017-0148-6Embryonic stem cellCollagen type ICyclic RGD peptideConfined compressionIntegrinsMechano-transduction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Olesja Hazenbiller Neil A. Duncan Roman J. Krawetz |
spellingShingle |
Olesja Hazenbiller Neil A. Duncan Roman J. Krawetz Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide BMC Cell Biology Embryonic stem cell Collagen type I Cyclic RGD peptide Confined compression Integrins Mechano-transduction |
author_facet |
Olesja Hazenbiller Neil A. Duncan Roman J. Krawetz |
author_sort |
Olesja Hazenbiller |
title |
Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide |
title_short |
Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide |
title_full |
Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide |
title_fullStr |
Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide |
title_full_unstemmed |
Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide |
title_sort |
reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or cyclo rgd peptide |
publisher |
BMC |
series |
BMC Cell Biology |
issn |
1471-2121 |
publishDate |
2017-11-01 |
description |
Abstract Background Self-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. Results The 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. Conclusions Overall, 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. |
topic |
Embryonic stem cell Collagen type I Cyclic RGD peptide Confined compression Integrins Mechano-transduction |
url |
http://link.springer.com/article/10.1186/s12860-017-0148-6 |
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