Single cell genomics over Waddington's landscape

3 Dec 2010

Junhyong Kim
Department of Biology and Penn Genomics Institute
University of Pennsylvania


The developmental biologist C.H. Waddington proposed a conceptual model of the "epigenetic landscape" using a metaphor of a ball rolling down a hill with various ridges and valleys. This metaphor encapsulates many concepts of development and differentiation including the idea of bifurcating decisions, multiple fates, and irreversible directional progress. Recent advances such as the iPS cells have revised these views, especially the concept of irreversible direction of differentiation. In the past four years, we have been working on the idea that differentiated cells represent quasi-stable states determined by a set of control parameters. We viewed RNA complement of a cell as a tunable control parameter that can be used to transdifferentiate one differentiated cell type into another cell type. In 2009 we demonstrated the use of whole transcriptome transfer to induce stable phenotypic conversion of a rat neuron into an astrocyte-like cell. In addition, we investigated the properties of individual cells within the RNA state space. Here, I discuss some of our experiments, conceptual models, and connect to ideas of Rene Thom who proposed that quasi-stable differentiated states represent stable dynamical flow separated by critical points.

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