Novel Markov model of induced pluripotency predicts gene expression changes in reprogramming.
BACKGROUND
Somatic cells can be reprogrammed to induced-pluripotent stem cells (iPSCs) by introducing few reprogramming factors, which challenges the long held view that cell differentiation is irreversible. However, the mechanism of induced pluripotency is still unknown.


METHODS
Inspired by the phenomenological reprogramming model of Artyomov et al (2010), we proposed a novel Markov model, stepwise reprogramming Markov (SRM) model, with simpler gene regulation rules and explored various properties of the model with Monte Carlo simulation. We calculated the reprogramming rate and showed that it would increase in the condition of knockdown of somatic transcription factors or inhibition of DNA methylation globally, consistent with the real reprogramming experiments. Furthermore, we demonstrated the utility of our model by testing it with the real dynamic gene expression data spanning across different intermediate stages in the iPS reprogramming process.


RESULTS
The gene expression data at several stages in reprogramming and the reprogramming rate under several typically experiment conditions coincided with our simulation results. The function of reprogramming factors and gene expression change during reprogramming could be partly explained by our model reasonably well.


CONCLUSIONS
This lands further support on our general rules of gene regulation network in iPSC reprogramming. This model may help uncover the basic mechanism of reprogramming and improve the efficiency of converting somatic cells to iPSCs.
MOE Key Laboratory of Bioinformatics and Bioinformatics Div, TNLIST /Department of Automation, Tsinghua University, Beijing 100084, China.
Zhirui
Z
Hu
Minping
M
Qian
Michael Q
MQ
Zhang
D002453:Cell Cycle; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D003198:Computer Simulation; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D008390:Markov Chains; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D014157:Transcription Factors