Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation

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 knowled...

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Main Authors: Chia-Chou Wu, Che Lin, Bor-Sen Chen
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2015/792843
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author Chia-Chou Wu
Che Lin
Bor-Sen Chen
author_facet Chia-Chou Wu
Che Lin
Bor-Sen Chen
author_sort Chia-Chou Wu
collection DOAJ
description 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.
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publishDate 2015-01-01
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spelling doaj-art-638b5b07914a4545a6a5a87cde4ea14d2025-02-03T06:06:16ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/792843792843Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed DifferentiationChia-Chou Wu0Che Lin1Bor-Sen Chen2Control and Systems Biology Laboratory, National Tsing Hua University, Hsinchu 30013, TaiwanInstitute of Communication, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanThe 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.http://dx.doi.org/10.1155/2015/792843
spellingShingle Chia-Chou Wu
Che Lin
Bor-Sen Chen
Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation
Stem Cells International
title Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation
title_full Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation
title_fullStr Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation
title_full_unstemmed Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation
title_short Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation
title_sort dynamic network based relevance score reveals essential proteins and functional modules in directed differentiation
url http://dx.doi.org/10.1155/2015/792843
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AT chelin dynamicnetworkbasedrelevancescorerevealsessentialproteinsandfunctionalmodulesindirecteddifferentiation
AT borsenchen dynamicnetworkbasedrelevancescorerevealsessentialproteinsandfunctionalmodulesindirecteddifferentiation