Using nanotopography and metabolomics to identify biochemical effectors of multipotency.
It is emerging that mesenchymal stem cell (MSC) metabolic activity may be a key regulator of multipotency. The metabolome represents a "snapshot" of the stem cell phenotype, and therefore metabolic profiling could, through a systems biology approach, offer and highlight critical biochemical pathways for investigation. To date, however, it has remained difficult to undertake unbiased experiments to study MSC multipotency in the absence of strategies to retain multipotency without recourse to soluble factors that can add artifact to experiments. Here we apply a nanotopographical systems approach linked to metabolomics to regulate plasticity and demonstrate rapid metabolite reorganization, allowing rational selection of key biochemical targets of self-renewal (ERK1/2, LDL, and Jnk). We then show that these signaling effectors regulate functional multipotency.
Centre for Cell Engineering, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK.
P Monica
PM
Tsimbouri
Rebecca J
RJ
McMurray
Karl V
KV
Burgess
Enateri V
EV
Alakpa
Paul M
PM
Reynolds
Kate
K
Murawski
Emmajayne
E
Kingham
Richard O C
RO
Oreffo
Nikolaj
N
Gadegaard
Matthew J
MJ
Dalby
D002478:Cells, Cultured; D006801:Humans; D055442:Metabolome / Q000502:physiology*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D020543:Proteome; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013499:Surface Properties
D020543:Proteome