Dynamic network-based relevance score reveals essential proteins and functional modules in directed differentiation
Journal
Stem Cells International
Journal Volume
2015
Date Issued
2015
Author(s)
Abstract
The induction of stem cells toward a desired differentiation direction is required for the advancement of stem cell-based therapies. Despite successful demonstrations of the control of differentiation direction, the effective use of stem cell-based therapies suffers from a lack of systematic knowledge regarding the mechanisms underlying directed differentiation. Using dynamic modeling and the temporal microarray data of three differentiation stages, three dynamic protein-protein interaction networks were constructed. The interaction difference networks derived from the constructed networks systematically delineated the evolution of interaction variations and the underlying mechanisms. A proposed relevance score identified the essential components in the directed differentiation. Inspection of well-known proteins and functional modules in the directed differentiation showed the plausibility of the proposed relevance score, with the higher scores of several proteins and function modules indicating their essential roles in the directed differentiation. During the differentiation process, the proteins and functional modules with higher relevance scores also became more specific to the neuronal identity. Ultimately, the essential components revealed by the relevance scores may play a role in controlling the direction of differentiation. In addition, these components may serve as a starting point for understanding the systematic mechanisms of directed differentiation and for increasing the efficiency of stem cell-based therapies. © 2015 Chia-Chou Wu et al.
Other Subjects
actin related protein; cadherin; fibroblast growth factor; fibroblast growth factor 8; hepatocyte nuclear factor 3beta; integrin; laminin; messenger RNA; Notch receptor; protein; protein CLDN1; protein CLDN3; protein EFEMP2; protein GLRX; protein METTL14; protein METTL3; protein MRPS34; protein NCOR2; protein NR2F2; protein POLR2I; protein STYXL1; Ras protein; septin 10; sonic hedgehog protein; transcription factor; transcription factor LMX1A; transcription factor Otx2; unclassified drug; unindexed drug; uvomorulin; Wnt protein; animal cell; Article; cell differentiation; cell proliferation; controlled study; Dynamic Network Based Relevance Score; embryonic stem cell; human; human cell; mathematical analysis; microarray analysis; mouse; nerve cell; nerve cell network; nonhuman; priority journal; protein function; protein protein interaction; rating scale; scoring system; stem cell transplantation
Type
journal article