A game of colonies: how is the balance of proliferation vs differentiation regulated in the human stem like cells?

Abstract

Stem cell self-renewal and differentiation regulate tissue homeostasis. We will develop a mathematical model to elucidate how key regulators of stem cell self-renewal, namely Wnt and Hippo signaling networks, influence cell commitment for differentiation. We have high-resolution and high-throughput datasets describing functional (intracellular calcium release, [Ca2+]i) and genomic (ChIP-seq, RNA-seq) characteristics in human cells. The motivation for this project is to integrate the genomic and functional biological parameters in a lattice based model. This will allow us to predict 1. how perturbations to these signaling networks interfere with the tissue structure and 2. how that can lead to disease.




References:
[1]

Schluter DK, Ramis-Conde I, Chaplain MAJ. 2015 Multi-scale modelling of the dynamics of cell colonies: insights into cell-adhesion forces and cancer invasion from in silico simulations. J. R. Soc. Interface (2014)

[2]

Thrasivoulou, C et al, Activation of Intracellular Calcium by Multiple Wnt Ligands and Translocation of β-Catenin into the Nucleus J. Biol. Chem (2013)

[3]

Jones, P.H. & Watt, F.M. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 73, 713-724 (1993).

[4]

Meng Z, Moroishi T, Guan KL. Mechanisms of Hippo pathway regulation. (2016)

[5]

Beaver CM, Ahmed A, Masters JR (2014) Clonogenicity: Holoclones and Meroclones Contain Stem Cells. PLoS ONE 9(2): e89834. doi: 10.1371/journal.pone.0089834


Biological Areas:

Cell Biology
Development

BBSRC Area:

Genes, development and STEM approaches to biology