IDEAS home Printed from https://ideas.repec.org/a/plo/pcbi00/1003165.html
   My bibliography  Save this article

Quantifying Cell Fate Decisions for Differentiation and Reprogramming of a Human Stem Cell Network: Landscape and Biological Paths

Author

Listed:
  • Chunhe Li
  • Jin Wang

Abstract

Cellular reprogramming has been recently intensively studied experimentally. We developed a global potential landscape and kinetic path framework to explore a human stem cell developmental network composed of 52 genes. We uncovered the underlying landscape for the stem cell network with two basins of attractions representing stem and differentiated cell states, quantified and exhibited the high dimensional biological paths for the differentiation and reprogramming process, connecting the stem cell state and differentiated cell state. Both the landscape and non-equilibrium curl flux determine the dynamics of cell differentiation jointly. Flux leads the kinetic paths to be deviated from the steepest descent gradient path, and the corresponding differentiation and reprogramming paths are irreversible. Quantification of paths allows us to find out how the differentiation and reprogramming occur and which important states they go through. We show the developmental process proceeds as moving from the stem cell basin of attraction to the differentiation basin of attraction. The landscape topography characterized by the barrier heights and transition rates quantitatively determine the global stability and kinetic speed of cell fate decision process for development. Through the global sensitivity analysis, we provided some specific predictions for the effects of key genes and regulation connections on the cellular differentiation or reprogramming process. Key links from sensitivity analysis and biological paths can be used to guide the differentiation designs or reprogramming tactics.Author Summary: Cellular differentiation and reprogramming have been extensively studied using experimental methods. We developed a landscape and kinetic path approach to explore the global stability of a stem cell developmental network. The cell fates are quantified by the basins of attractions of the underlying landscape. The developmental process can be quantitatively described and uncovered by the biological paths on the landscape from the progenitor state to the differentiation state. This allows us to trace the underlying detailed kinetic process and obtain the recipe for engineering differentiation and reprogramming. By quantifying the landscape topography by the barrier heights and dynamic transition speed, we can evaluate the stability and kinetics of cell fate decision making process of the development and reprogramming. The global sensitivity analysis provided predictions about the effects of the key genes and regulation links of the network on the stability of differentiation and reprogramming process. This can be tested in the experiments. Results from sensitivity analysis and biological paths acquired can be used to guide the differentiation designs or reprogramming tactics.

Suggested Citation

  • Chunhe Li & Jin Wang, 2013. "Quantifying Cell Fate Decisions for Differentiation and Reprogramming of a Human Stem Cell Network: Landscape and Biological Paths," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-14, August.
    • Handle: RePEc:plo:pcbi00:1003165
    DOI: 10.1371/journal.pcbi.1003165
    as

    Download full text from publisher

    File URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003165
    Download Restriction: no
    File URL: https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1003165&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pcbi.1003165?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Shinya Yamanaka, 2009. "Elite and stochastic models for induced pluripotent stem cell generation," Nature, Nature, vol. 460(7251), pages 49-52, July.
    2. Thomas Graf & Tariq Enver, 2009. "Forcing cells to change lineages," Nature, Nature, vol. 462(7273), pages 587-594, December.
    3. Chunhe Li & Erkang Wang & Jin Wang, 2011. "Potential Landscape and Probabilistic Flux of a Predator Prey Network," PLOS ONE, Public Library of Science, vol. 6(3), pages 1-9, March.
    4. Shinya Yamanaka & Helen M. Blau, 2010. "Nuclear reprogramming to a pluripotent state by three approaches," Nature, Nature, vol. 465(7299), pages 704-712, June.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Rowan D Brackston & Eszter Lakatos & Michael P H Stumpf, 2018. "Transition state characteristics during cell differentiation," PLOS Computational Biology, Public Library of Science, vol. 14(9), pages 1-24, September.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Rowan D Brackston & Eszter Lakatos & Michael P H Stumpf, 2018. "Transition state characteristics during cell differentiation," PLOS Computational Biology, Public Library of Science, vol. 14(9), pages 1-24, September.
    2. Wio, H.S. & Deza, J.I. & Sánchez, A.D. & García-García, R. & Gallego, R. & Revelli, J.A. & Deza, R.R., 2022. "The nonequilibrium potential today: A short review," Chaos, Solitons & Fractals, Elsevier, vol. 165(P1).
    3. Anyou Wang & Ying Du & Qianchuan He & Chunxiao Zhou, 2013. "A Quantitative System for Discriminating Induced Pluripotent Stem Cells, Embryonic Stem Cells and Somatic Cells," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-10, February.
    4. Francesco Panariello & Onelia Gagliano & Camilla Luni & Antonio Grimaldi & Silvia Angiolillo & Wei Qin & Anna Manfredi & Patrizia Annunziata & Shaked Slovin & Lorenzo Vaccaro & Sara Riccardo & Valenti, 2023. "Cellular population dynamics shape the route to human pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Wei Li & Qi Long & Hao Wu & Yanshuang Zhou & Lifan Duan & Hao Yuan & Yingzhe Ding & Yile Huang & Yi Wu & Jinyu Huang & Delong Liu & Baodan Chen & Jian Zhang & Juntao Qi & Shiwei Du & Linpeng Li & Yang, 2022. "Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Ruimin Xu & Qianshu Zhu & Yuyan Zhao & Mo Chen & Lingyue Yang & Shijun Shen & Guang Yang & Zhifei Shi & Xiaolei Zhang & Qi Shi & Xiaochen Kou & Yanhong Zhao & Hong Wang & Cizhong Jiang & Chong Li & Sh, 2023. "Unreprogrammed H3K9me3 prevents minor zygotic genome activation and lineage commitment in SCNT embryos," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Tian Hong & Jianhua Xing & Liwu Li & John J Tyson, 2011. "A Mathematical Model for the Reciprocal Differentiation of T Helper 17 Cells and Induced Regulatory T Cells," PLOS Computational Biology, Public Library of Science, vol. 7(7), pages 1-13, July.
    8. María José Pino-Barrio & Elisa García-García & Pablo Menéndez & Alberto Martínez-Serrano, 2015. "V-Myc Immortalizes Human Neural Stem Cells in the Absence of Pluripotency-Associated Traits," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-13, March.
    9. Rabajante, Jomar Fajardo & Talaue, Cherryl Ortega, 2015. "Equilibrium switching and mathematical properties of nonlinear interaction networks with concurrent antagonism and self-stimulation," Chaos, Solitons & Fractals, Elsevier, vol. 73(C), pages 166-182.
    10. Gleb Zyuz’kov, 2019. "The Foresight for Practical Realization of Research in Regenerative Medicine and Cell Technologies," Science Governance and Scientometrics Journal, Russian Research Institute of Economics, Politics and Law in Science and Technology (RIEPL), vol. 14(1), pages 42-69, March.
    11. Maria Arez & Melanie Eckersley-Maslin & Tajda Klobučar & João Gilsa Lopes & Felix Krueger & Annalisa Mupo & Ana Cláudia Raposo & David Oxley & Samantha Mancino & Anne-Valerie Gendrel & Bruno Bernardes, 2022. "Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    12. Michaela Luconi & Miguel A. Sogorb & Udo R. Markert & Emilio Benfenati & Tobias May & Susanne Wolbank & Alessandra Roncaglioni & Astrid Schmidt & Marco Straccia & Sabrina Tait, 2022. "Human-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto–Placental Organ-on-Chip Platform," IJERPH, MDPI, vol. 19(23), pages 1-31, November.
    13. Nazifa Ahmed Moumi & Badhan Das & Zarin Tasnim Promi & Nishat Anjum Bristy & Md Shamsuzzoha Bayzid, 2019. "Quartet-based inference of cell differentiation trees from ChIP-Seq histone modification data," PLOS ONE, Public Library of Science, vol. 14(9), pages 1-25, September.
    14. Yan, Kexun & Wang, Maoxiang & Hu, Fenglan & Xu, Meng, 2023. "Effect of cellular dedifferentiation on the growth of cell lineages," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 632(P1).
    15. Margaret J Tse & Brian K Chu & Cameron P Gallivan & Elizabeth L Read, 2018. "Rare-event sampling of epigenetic landscapes and phenotype transitions," PLOS Computational Biology, Public Library of Science, vol. 14(8), pages 1-28, August.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pcbi00:1003165. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: ploscompbiol (email available below). General contact details of provider: https://journals.plos.org/ploscompbiol/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.