How does gene expression entropy change along developmental trajectories?

Elisabeth Roesch⁰, Anissa Guillemin⁰, Michael P.H. Stumpf⁰, Megan Anne Coomer⁰
(0) University of Melbourne

Find me on Tues Nov 24th, 1:40-3pm AEDT in Remo, table 109

Abstract
The differentiation of stem or progenitor cells is accompanied by profound changes in gene expression. In addition to overall changes in expression profiles there is also widespread evidence that also the variability of gene expression varies along the developmental trajectory [1]. Here we investigate this in the context of simple mathematical models. These models are inspired by, and share important features with Waddington’s epigenetic landscape [2], and they allow us to disentangle the effects of developmental dynamics and molecular noise on patterns of gene expression variability [3], and to investigate the role of molecular noise in the cell fate decision making process.

In particular we consider dynamical systems that exhibit the types of qualitative change — “bifurcations” in the language of dynamical systems — that occur in e.g. stem cell differentiation and developmental patterning processes. Using simulations we construct the corresponding epigenetic landscapes and we show how noise can affect, and even mask some types of bifurcations. Noise, we show, affects the shape of the epigenetic landscape. Indeed, landscapes for the same developmental system, but with different levels of molecular noise can give rise to qualitatively different behaviour and outcomes.
This analysis complements ongoing efforts by developmental biologists and the single cell analysis community to distill features of cell differentiation dynamics from data directly. We conclude by pointing out, how these modelling studies can help in the analysis of single cell transcriptomic data.



[1] Angelique Richard, Lois Boullu, Ulysse Herbach, Arnaud Bonnafoux, Valerie Morin, Elodie Vallin, Anissa Guillemin, Nan Papili Gao, Rudiyanto Gunawan, Jeremie Cosette, Ophelie Arnaud, Jean-Jacques Kupiec, Thibault Espinasse, Sandrine Gonin-Giraud, and Olivier Gandrillon. Single-Cell Based Analysis Highlights a Surge in Cell-to-Cell Molecular Variability Preceding Irreversible Commitment in a Differentiation Process. PLOS Biology, 2016.
[2] Conrad Hal Waddington. The strategy of the genes. Allen & Unwin, 1957.
[3] Naomi Moris, Cristina Pina, and Alfonso Martinez Arias. Transition states and cell fate decisions in epigenetic landscapes. Nature Reviews Genetics, 2016.