Written by Catharine Paddock PhD
In a Nature Genetics paper, the team – led by scientists from the University of Bristol in the UK – notes that the current method for directly reprogramming human cells from one type to another – called “cell transdifferentiation” – takes a long time because it relies on trial and error to find the correct transcription factors.
Transcription factors are proteins that – among other things – help to regulate gene expression. All the cells of our body carry the same genes, but different genes are expressed and silenced in different cell types.
To transdifferentiate one cell into another, you have to change the arrangement of which genes are switched on and which are switched off – and for this, you need a unique set of transcription factors, depending on which genes you are dealing with.
There is another way to create new cells of a certain type, and that is to go via pluripotent stem cells – immature or precursor cells that have not yet “decided” which type of cell they are. But, as Julian Gough – professor of bioinformatics at Bristol – explains, their predictive system means you do not have to go down this path:
“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 can be used to treat many different medical conditions and diseases. There are two types: embryonic and artificial. Embryonic stem cells are derived from embryos, and while they are the best quality stem cells, there are ethical concerns about their use – plus, the process of harvesting them from embryos for therapeutic use is expensive and difficult.
The first human artificial pluripotent stem cells were created nearly a decade ago by a team led by Shinya Yamanaka, of Kyoto University in Japan. It took them a long time – using trial and error – to find the four transcription factors that allowed them to reprogram fibroblasts from the skin of mice into pluripotent stem cells. Since then, scientists have only been able to discover further conversions for human cells a handful of times.
‘Atlas of cellular reprogramming’
