title: Biophysical regulation of epigenetic state and cell reprogramming.
abstract: Biochemical factors can help reprogram somatic cells into pluripotent stem cells, yet the role of biophysical factors during reprogramming is unknown. Here, we show that biophysical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells' epigenetic state. Specifically, decreased histone deacetylase activity and upregulation of the expression of WD repeat domain 5 (WDR5)--a subunit of H3 methyltranferase--by microgrooved surfaces lead to increased histone H3 acetylation and methylation. We also show that microtopography promotes a mesenchymal-to-epithelial transition in adult fibroblasts. Nanofibrous scaffolds with aligned fibre orientation produce effects similar to those produced by microgrooves, suggesting that changes in cell morphology may be responsible for modulation of the epigenetic state. These findings have important implications in cell biology and in the optimization of biomaterials for cell-engineering applications.
authors.affiliation: 1] UC Berkeley & UCSF Joint Graduate Program in Bioengineering, Berkeley/San Francisco, California 94720/94143, USA [2] Department of Bioengineering, University of California, Berkeley, B108A Stanley Hall, Berkeley, California 94720-1762, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Downing
authors.forename: Jennifer
authors.initials: J
authors.lastname: Soto
authors.forename: Constant
authors.initials: C
authors.lastname: Morez
authors.forename: Timothee
authors.initials: T
authors.lastname: Houssin
authors.forename: Ashley
authors.initials: A
authors.lastname: Fritz
authors.forename: Falei
authors.initials: F
authors.lastname: Yuan
authors.forename: Julia
authors.initials: J
authors.lastname: Chu
authors.forename: Shyam
authors.initials: S
authors.lastname: Patel
authors.forename: David V
authors.initials: DV
authors.lastname: Schaffer
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D000199:Actins / Q000737:chemistry; D000215:Acylation; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D060846:Cell Engineering / Q000379:methods; D048430:Cell Shape; D044127:Epigenesis, Genetic; D004848:Epithelium / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000473:pathology; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009218:Myosins / Q000737:chemistry; D036103:Nanotechnology; D013499:Surface Properties
chemical_list: D000199:Actins; D001672:Biocompatible Materials; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C502547:WDR5 protein, human; D011495:Histone-Lysine N-Methyltransferase; D009218:Myosins