University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Science
  • School of Mathematics and Statistics
  • School of Mathematics and Statistics - Research Publications
  • View Item
  • Minerva Access
  • Science
  • School of Mathematics and Statistics
  • School of Mathematics and Statistics - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Mathematical modeling of GATA-switching for regulating the differentiation of hematopoietic stem cell

    Thumbnail
    Download
    published version (1.928Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    25
    21
    Author
    Tian, T; Smith-Miles, K
    Date
    2014-01-24
    Source Title
    BMC Systems Biology
    Publisher
    BIOMED CENTRAL LTD
    University of Melbourne Author/s
    Smith-Miles, Kate
    Affiliation
    School of Mathematics and Statistics
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Tian, T. & Smith-Miles, K. (2014). Mathematical modeling of GATA-switching for regulating the differentiation of hematopoietic stem cell. BMC SYSTEMS BIOLOGY, 8 (Suppl 1), https://doi.org/10.1186/1752-0509-8-S1-S8.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256800
    DOI
    10.1186/1752-0509-8-S1-S8
    Abstract
    BACKGROUND: Hematopoiesis is a highly orchestrated developmental process that comprises various developmental stages of the hematopoietic stem cells (HSCs). During development, the decision to leave the self-renewing state and selection of a differentiation pathway is regulated by a number of transcription factors. Among them, genes GATA-1 and PU.1 form a core negative feedback module to regulate the genetic switching between the cell fate choices of HSCs. Although extensive experimental studies have revealed the mechanisms to regulate the expression of these two genes, it is still unclear how this simple module regulates the genetic switching. METHODS: In this work we proposed a mathematical model to study the mechanisms of the GATA-PU.1 gene network in the determination of HSC differentiation pathways. We incorporated the mechanisms of GATA switch into the module, and developed a mathematical model that comprises three genes GATA-1, GATA-2 and PU.1. In addition, a novel multiple-objective optimization method was designed to infer unknown parameters in the proposed model by realizing different experimental observations. A stochastic model was also designed to describe the critical function of noise, due to the small copy numbers of molecular species, in determining the differentiation pathways. RESULTS: The proposed deterministic model has successfully realized three stable steady states representing the priming and different progenitor cells as well as genetic switching between the genetic states under various experimental conditions. Using different values of GATA-1 synthesis rate for the GATA-1 protein availability in the chromatin sites during the time period of GATA switch, stochastic simulations for the first time have realized different proportions of cells leading to different developmental pathways under various experimental conditions. CONCLUSIONS: Mathematical models provide testable predictions regarding the mechanisms and conditions for realizing different differentiation pathways of hematopoietic stem cells. This work represents the first attempt at using a discrete stochastic model to realize the decision of HSC differentiation pathways showing a multimodal distribution.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45689]
    • School of Mathematics and Statistics - Research Publications [680]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors