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Analysis of regulatory network involved in mechanical induction of embryonic stem cell differentiation

Zhang, X and Jaramillo, M and Singh, S and Kumta, P and Banerjee, I (2012) Analysis of regulatory network involved in mechanical induction of embryonic stem cell differentiation. PLoS ONE, 7 (4).

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Embryonic stem cells are conventionally differentiated by modulating specific growth factors in the cell culture media. Recently the effect of cellular mechanical microenvironment in inducing phenotype specific differentiation has attracted considerable attention. We have shown the possibility of inducing endoderm differentiation by culturing the stem cells on fibrin substrates of specific stiffness [1]. Here, we analyze the regulatory network involved in such mechanically induced endoderm differentiation under two different experimental configurations of 2-dimensional and 3-dimensional culture, respectively. Mouse embryonic stem cells are differentiated on an array of substrates of varying mechanical properties and analyzed for relevant endoderm markers. The experimental data set is further analyzed for identification of co-regulated transcription factors across different substrate conditions using the technique of bi-clustering. Overlapped bi-clusters are identified following an optimization formulation, which is solved using an evolutionary algorithm. While typically such analysis is performed at the mean value of expression data across experimental repeats, the variability of stem cell systems reduces the confidence on such analysis of mean data. Bootstrapping technique is thus integrated with the bi-clustering algorithm to determine sets of robust bi-clusters, which is found to differ significantly from corresponding bi-clusters at the mean data value. Analysis of robust bi-clusters reveals an overall similar network interaction as has been reported for chemically induced endoderm or endodermal organs but with differences in patterning between 2-dimensional and 3-dimensional culture. Such analysis sheds light on the pathway of stem cell differentiation indicating the prospect of the two culture configurations for further maturation. © 2012 Zhang et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Zhang, X
Jaramillo, M
Singh, S
Kumta, Ppkumta@pitt.eduPKUMTA0000-0003-1227-1249
Banerjee, Iipb1@pitt.eduIPB1
ContributionContributors NameEmailPitt UsernameORCID
Date: 27 April 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0035700
Schools and Programs: Swanson School of Engineering > Bioengineering
Swanson School of Engineering > Chemical Engineering
Swanson School of Engineering > Mechanical Engineering
Refereed: Yes
Other ID: NLM PMC3338716
PubMed Central ID: PMC3338716
PubMed ID: 22558203
Date Deposited: 24 Sep 2012 20:21
Last Modified: 05 Feb 2019 17:55


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