PMID- 23312853 OWN - NLM STAT- MEDLINE DCOM- 20130722 LR - 20220310 IS - 1878-5905 (Electronic) IS - 0142-9612 (Print) IS - 0142-9612 (Linking) VI - 34 IP - 9 DP - 2013 Mar TI - A genomics approach in determining nanotopographical effects on MSC phenotype. PG - 2177-84 LID - S0142-9612(12)01399-3 [pii] LID - 10.1016/j.biomaterials.2012.12.019 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Tsimbouri, Penelope M AU - Tsimbouri PM AD - Centre for Cell Engineering, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK. penelope.tsimbouri@glasgow.ac.uk FAU - Murawski, Kate AU - Murawski K FAU - Hamilton, Graham AU - Hamilton G FAU - Herzyk, Pawel AU - Herzyk P FAU - Oreffo, Richard O C AU - Oreffo RO FAU - Gadegaard, Nikolaj AU - Gadegaard N FAU - Dalby, Matthew J AU - Dalby MJ LA - eng GR - BB/G006970/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/G008868/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130109 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 SB - IM MH - Blotting, Western MH - Cell Adhesion MH - Cell Differentiation MH - Cells, Cultured MH - Gene Expression Regulation MH - Genomics/*methods MH - Humans MH - In Situ Hybridization, Fluorescence MH - Mechanotransduction, Cellular MH - Mesenchymal Stem Cells/*cytology MH - Nanotechnology/*methods MH - *Phenotype MH - Real-Time Polymerase Chain Reaction MH - Regenerative Medicine/methods PMC - PMC3573234 EDAT- 2013/01/15 06:00 MHDA- 2013/07/23 06:00 PMCR- 2013/03/01 CRDT- 2013/01/15 06:00 PHST- 2012/09/10 00:00 [received] PHST- 2012/12/15 00:00 [accepted] PHST- 2013/01/15 06:00 [entrez] PHST- 2013/01/15 06:00 [pubmed] PHST- 2013/07/23 06:00 [medline] PHST- 2013/03/01 00:00 [pmc-release] AID - S0142-9612(12)01399-3 [pii] AID - 10.1016/j.biomaterials.2012.12.019 [doi] PST - ppublish SO - Biomaterials. 2013 Mar;34(9):2177-84. doi: 10.1016/j.biomaterials.2012.12.019. Epub 2013 Jan 9.