A Research Blog

In 2006, Japanese scientist Shinya Yamanaka and colleagues discovered that mature cells can be reprogrammed and reverted to a stem-cell-like state. Known as induced pluripotent cells (iPSCs), these cells have the ability to develop into any cell type. This discovery was stunning enough that Yamanaka was awarded the 2012 Nobel Prize in Physiology or Medicine for his revolutionary work on reprogramming adult cells, and spurred thousands of related publications.Owen

The field of reprogramming has generated a lot of excitement in recent years because iPSCs are a revolution in regenerative medicine, which seeks to replace tissue or organs damaged by disease, trauma, or congenital issues. In addition, reprogramming presents the possibility that we could generate patient-specific cell-types to model disease or use as a cell therapy. However, in order to be able to utilise these cells to their fullest extent, it is important that we fully understand the reprogramming process. To do this we need to study the process starting from many different cell types, not only from a single source. To date, fibroblasts have most often been used as a source cell type for reprogramming simply because they are easy to acquire and manipulate. In other words, fibroblasts was chosen for convenience rather than because of an important biological role in reprogramming. As such, much of what we know about this process is derived from work on fibroblasts and we assume that what we have learned from this conversion also holds true for other cell types.

Duke-NUS Assistant Professor Owen Rackham and his team in collaboration with Prof Jose Polo from Monash University in Australia found that this assumption was not true: The reprogramming process varies greatly depending on which cell type you start with. They studied three different cell types: a fibroblast, a neutrophil and a keratinocyte, and found that the process varies greatly both in terms of the time required and the order in which important events in the reprogramming occur.

Their study was recently published in Cell Reports. They also showed that the normal measure that a reprogramming experiment is complete (i.e. measuring Oct4 expression) is not valid for all cell types. Their results will help other scientists to get a better understanding of the biology of reprogramming, a critical step to developing safe and effective regenerative medicines.

This is the first study of its kind. Prior to this, very little work has been done to understand the effect of the starting cell type on reprogramming, and almost all prior research was from studying conversions using fibroblasts. 

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