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A genomics approach in determining nanotopographical effects on MSC phenotype

A genomics approach in determining nanotopographical effects on MSC phenotype
A genomics approach in determining nanotopographical effects on MSC phenotype
Topography and its effects on cell adhesion, morphology, growth and differentiation are well documented. Thus, current advances with the use of nanotopographies offer promising results in the field of regenerative medicine. Studies have also shown nanotopographies to have strong effects on stem cell self-renewal and differentiation. What is less clear however is what mechanotransductive mechanisms are employed by the cells to facilitate such changes. In fastidious cell types, it has been suggested that direct mechanotransduction producing morphological changes in the nucleus, nucleoskeleton and chromosomes themselves may be central to cell responses to topography. In this report we move these studies into human skeletal or mesenchymal stem cells and propose that direct (mechanical) signalling is important in the early stages of tuning stem cell fate to nanotopography. Using fluorescence in situ hybridization (FISH) and Affymetrix arrays we have evidence that nanotopography stimulates changes in nuclear organisation that can be linked to spatially regulated genes expression with a particular focus on phenotypical genes. For example, chromosome 1 was seen to display the largest numbers of gene deregulations and also a concomitant change in nuclear positioning in response to nanotopography. Plotting of deregulated genes in reference to band positioning showed that topographically related changes tend to happen towards the telomeric ends of the chromosomes, where bone related genes are generally clustered. Such an approach offers a better understanding of cell-surface interaction and, critically, provides new insights of how to control stem cell differentiation with future applications in areas including regenerative medicine.
0142-9612
2177-2184
Tsimbouri, P.M.
e47e799a-143e-4436-967d-41b920f785ae
Murawski, Kate
af6e59f5-f9db-47a6-a479-34d967a88064
Hamilton, Graham
24ce98c0-3d40-4349-ad40-5124b26e6751
Herzyk, Pawel
cef75f09-fa0b-4da4-9050-37df18da040b
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Gadegaard, Nikolaj
bf72c3d1-e6a7-48b4-a968-c496b655bd98
Dalby, Matthew J.
25dcae6a-8289-4169-abb7-c45fff0bafdc
Tsimbouri, P.M.
e47e799a-143e-4436-967d-41b920f785ae
Murawski, Kate
af6e59f5-f9db-47a6-a479-34d967a88064
Hamilton, Graham
24ce98c0-3d40-4349-ad40-5124b26e6751
Herzyk, Pawel
cef75f09-fa0b-4da4-9050-37df18da040b
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Gadegaard, Nikolaj
bf72c3d1-e6a7-48b4-a968-c496b655bd98
Dalby, Matthew J.
25dcae6a-8289-4169-abb7-c45fff0bafdc

Tsimbouri, P.M., Murawski, Kate, Hamilton, Graham, Herzyk, Pawel, Oreffo, Richard O.C., Gadegaard, Nikolaj and Dalby, Matthew J. (2013) A genomics approach in determining nanotopographical effects on MSC phenotype. Biomaterials, 34 (9), 2177-2184. (doi:10.1016/j.biomaterials.2012.12.019). (PMID:23312853)

Record type: Article

Abstract

Topography and its effects on cell adhesion, morphology, growth and differentiation are well documented. Thus, current advances with the use of nanotopographies offer promising results in the field of regenerative medicine. Studies have also shown nanotopographies to have strong effects on stem cell self-renewal and differentiation. What is less clear however is what mechanotransductive mechanisms are employed by the cells to facilitate such changes. In fastidious cell types, it has been suggested that direct mechanotransduction producing morphological changes in the nucleus, nucleoskeleton and chromosomes themselves may be central to cell responses to topography. In this report we move these studies into human skeletal or mesenchymal stem cells and propose that direct (mechanical) signalling is important in the early stages of tuning stem cell fate to nanotopography. Using fluorescence in situ hybridization (FISH) and Affymetrix arrays we have evidence that nanotopography stimulates changes in nuclear organisation that can be linked to spatially regulated genes expression with a particular focus on phenotypical genes. For example, chromosome 1 was seen to display the largest numbers of gene deregulations and also a concomitant change in nuclear positioning in response to nanotopography. Plotting of deregulated genes in reference to band positioning showed that topographically related changes tend to happen towards the telomeric ends of the chromosomes, where bone related genes are generally clustered. Such an approach offers a better understanding of cell-surface interaction and, critically, provides new insights of how to control stem cell differentiation with future applications in areas including regenerative medicine.

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Published date: 8 January 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 347330
URI: http://eprints.soton.ac.uk/id/eprint/347330
ISSN: 0142-9612
PURE UUID: 13c80574-ccbd-42a7-80b3-571d1fd8fd1e
ORCID for Richard O.C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 21 Jan 2013 12:39
Last modified: 27 Oct 2023 01:41

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Contributors

Author: P.M. Tsimbouri
Author: Kate Murawski
Author: Graham Hamilton
Author: Pawel Herzyk
Author: Nikolaj Gadegaard
Author: Matthew J. Dalby

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