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BMC Syst Biol. 2017 Oct 3;11(Suppl 5):91. doi: 10.1186/s12918-017-0467-4.

System modeling reveals the molecular mechanisms of HSC cell cycle alteration mediated by Maff and Egr3 under leukemia.

Author information

1
Center for Computational Biology and Bioinformatics, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
2
Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200031, China.
3
Shanghai Center for Bioinformatics Technology, Shanghai, 201203, China.
4
Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.
5
Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200031, China. liulei@fudan.edu.cn.
6
Shanghai Center for Bioinformatics Technology, Shanghai, 201203, China. liulei@fudan.edu.cn.

Abstract

BACKGROUND:

Molecular mechanisms of the functional alteration of hematopoietic stem cells (HSCs) in leukemic environment attract intensive research interests. As known in previous researches, Maff and Egr3 are two important genes having opposite functions on cell cycle; however, they are both highly expressed in HSCs under leukemia. Hence, exploring the molecular mechanisms of how the genes act on cell cycle will help revealing the functional alteration of HSCs.

RESULTS:

We herein utilize the bioinformatic resources to computationally model the acting mechanisms of Maff and Egr3 on cell cycle. Using the data of functional experiments as reference, molecular acting mechanisms are optimally enumerated through model selection. The results are consolidated by evidences from gene sequence analysis, thus having enhanced the confidence of our pilot findings, which suggest that HSCs possibly undergo a "adaptation - suppression" process in response to the malignant environment of leukemia.

CONCLUSION:

As a pilot research, our results may provide valuable insights for further experimental studies. Meanwhile, our research method combining computational modeling and data from functional experiments can be worthwhile for knowledge discovery; and it can be generalized and extended to other biological/biomedical studies.

KEYWORDS:

Hematopoietic stem cells; Leukemia; Maff and Egr3; Model selection; System modeling

PMID:
28984203
PMCID:
PMC5629552
DOI:
10.1186/s12918-017-0467-4
[Indexed for MEDLINE]
Free PMC Article

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