News

Unraveling the biological mystery of how cells regulate their fate

13 February 2015
Christine Wells and Ernst Wolvetang

Stem Cells Australia researchers – Professor Christine Wells and Professor Ernst Wolvetang – are part of an international consortium that has been able to shed light on how mammalian cells transition from one type to another during development and in response to stress or infection.

In the work, published today in the prestigious journal Science, researchers were able to show the importance of a key regulatory “switch” involved in triggering a cascade of genetic changes that ultimately result in dramatic change in the attributes of the cell.

While scientists have long recognized that activation of particular genes in a cell were controlled by two different mechanisms encoded in the cell’s DNA – enhancers and promoters – exactly how these molecular tools influenced gene expression remained unclear.

By conducting a comprehensive analysis of many different types of human and mouse cells, researchers were able to show that it is the enhancers – regions of DNA often located a long way from the actual genes of interest activation – that were crucial to coordinating rapid changes in gene expression.

Commenting on the significance of this work, Professor Martin Pera Chair of Stem Cells Science at The University of Melbourne and Program Leader of Stem Cells Australia said, “This landmark study uncovers striking new features of gene regulation in mammalian cells.  

The results show that when cells switch on new genes, this process starts from enhancer regions, key regulatory elements throughout the genome.  The study indicates that this enhancer-based transcription is an essential first phase of gene activation when stem cells differentiate. The results of this study will change our understanding of how stem cells transition into new cell types, and will help us to understand disorders of human development.“

In order to conduct this study, scientists from 114 institutes and in more than 20 countries joined forces. This work builds on previous discoveries made by the Japanese-led Functional Annotation of the Mammalian Genome (FANTOM5) consortium.

The Australian contribution to this work included Christine Wells from The University of Queensland who is a founding member of the FANTOM5 initiative and helped direct the overall study. Together with Ernst Wolvetang also from The University of Queensland, they carried out a detailed and careful analysis of the differentiation of human pluripotent stem cell differentiation into the neural lineage.  

Other Australian based scientists involved in this work were Professor Alistair Forrest at the Harry Perkins Institute of Medical Research who is also scientific coordinator of the FANTOM5 project; Professor Peter Klinken, Western Australia’s Chief Scientist; Dr Louise Winteringham at the Harry Perkins Institute of Medical Research; and Dr Timo Lassmann at the Telethon Institute for Child Health Research.

Click here to view paper: Arner E et al. (2015) Enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science [DOI: 10.1126/science.1259418].

For more information:
Future cancer treatments may target DNA 'organisers' [The Australian, 13 February 2015]
FANTOM5 project discovers general rules governing how cells change [13 February 2015]