MOGRIFY pubblicazione scientifica
MOGRIFY A predictive computational framework for direct reprogramming between human cell types
- Owen J L Rackham,
- Jaber Firas,
- Hai Fang,
- Matt E Oates,
- Melissa L Holmes,
- Anja S Knaupp,
- The FANTOM Consortium,
- Harukazu Suzuki,
- Christian M Nefzger,
- Carsten O Daub,
- Jay W Shin,
- Enrico Petretto,
- Alistair R R Forrest,
- Yoshihide Hayashizaki,
- Jose M Polo
- & Julian Gough
Transdifferentiation, the process of converting from one cell type to another without going through a pluripotent state, has great promise for regenerative medicine. The identification of key transcription factors for reprogramming is currently limited by the cost of exhaustive experimental testing of plausible sets of factors, an approach that is inefficient and unscalable. Here we present a predictive system (Mogrify) that combines gene expression data with regulatory network information to predict the reprogramming factors necessary to induce cell conversion. We have applied Mogrify to 173 human cell types and 134 tissues, defining an atlas of cellular reprogramming. Mogrify correctly predicts the transcription factors used in known transdifferentiations. Furthermore, we validated two new transdifferentiations predicted by Mogrify. We provide a practical and efficient mechanism for systematically implementing novel cell conversions, facilitating the generalization of reprogramming of human cells. Predictions are made available to help rapidly further the field of cell conversion.
Breakthrough in human cell transformation could revolutionize regenerative medicine
by Staff Writers
Bristol, UK (SPX) Jan 20, 2016
A breakthrough in the transformation of human cells by an international team led by researchers at the University of Bristol could open the door to a new range of treatments for a variety of medical conditions. Their paper, published in Nature Genetics, demonstrates the creation of a system that predicts how to create any human cell type from another cell type directly, without the need for experimental trial and error.
Julian Gough, professor of bioinformatics at the University of Bristol, said: 'The barrier to progress in this field is the very limited types of cells scientists are able to produce. Our system, Mogrify, is a bioinformatics resource that will allow experimental biologists to bypass the need to create stem cells.'
Pluripotent stem cells - or cells that have not yet 'decided' what to become - can be used to treat many different medical conditions and diseases. The first human artificial pluripotent stem cells were created by Japanese researcher Shinya Yamanaka in 2007, through a process of educated trial and error that took a long time. In the nine years since, scientists have only been able to discover further conversions for human cells a handful of times.
Professor Gough said: 'Mogrify predicts how to create any human cell type from any other cell type directly. With Professor Jose Polo at Monash University in Australia, we tested it on two new human cell conversions, and succeeded first time for both. The speed with which this was achieved suggests Mogrify will enable the creation of a great number of human cell types in the lab.'
'The ability to produce numerous types of human cells will lead directly to tissue therapies of all kinds, to treat conditions from arthritis to macular degeneration, to heart disease. The fuller understanding, at the molecular level of cell production leading on from this, may allow us to grow whole organs from somebody's own cells.
'This represents a significant breakthrough in regenerative medicine, and paves the way for life-changing medical advances within a few years from now, and the possibility in the longer term of improving the quality of longer lives, as well as making them longer.'
To achieve this game-changing result, Professor Gough worked with then-PhD student Dr Owen Rackham (who now works at Duke-NUS Medical School in Singapore) for five years to develop a computational algorithm to predict the cellular factors for cell conversions. The algorithm was conceived from data collected as a part of the FANTOM international consortium (based at RIKEN, Japan) of which Professor Gough is a long time member.
The algorithm, called Mogrify, has been made available online for other researchers and scientists, so that the field may advance rapidly.
The research team comprised collaborators from Bristol, Australia, Singapore, and Japan. Research paper: 'Mogrify: An Atlas for Direct Reprogramming Between Human Cell Types' by Rackham et al in Nature Genetics.