Remember Project Grandiose led by the great stem cell scientist Andras Nagy?
It’s a massive project intended to decipher what makes stem cells tick and how ordinary cells be changed or reprogrammed into powerful pluripotent stem cells that can make any other type of cell.
I’ve heard Nagy speak before about it at meetings and this blog first reported on these fuzzy cells last year here (Jailbreaking Cell Fate Reprograms to Multiple Stem Cell Types, Says Nagy, Not Just iPS cells).
This “think big” Grandiose team has come out today with five new papers in Nature and Nature Communications on the fuzzy new type of stem cell fitting into the most powerful pluripotent class of stem cells.
The team calls these new cells “F-class’ because the colonies that they make in a dish are fuzzy compared to the compact colony type more commonly seen in pluripotent cultures of ES cells or induced pluripotent stem cells (IPSC). See image above from one of the papers from the Grandiose team.
F-class pluripotent cells are an interesting new type of pluripotent stem cell. While these cells appear to be relatives of IPSC and of ES cells, they have some potentially important differences as well such as requiring sustained reprogramming factor expression to maintain their identity. F-class cells also have some differences in gene expression and in their epigenomes compared to other types of pluripotent cells. For example, specific histone lysine methylation (H3K27me3) and DNA methylation are implicated.
The quintet of papers from Project Grandiose together report an amazingly large amount of data (you can see the actual data here) on both F-class cells and reprogramming more generally fitting with the “Grandiose” name. This data is like a Buffalo snowstorm so it will take some time for the field to “dig out” and dig into the drifts of data to entirely digest the meaning of it all, but it seems to be a major step forward in understanding controllable pluripotent states.
Some exciting questions remain for future studies.
Can human F-class cells be produced?
The team shows that F-class cells have some differentiation potential, but I’d like to learn a lot more about how these cells differentiate into specific types of functional cells compared to those produced from ES cells and IPSC.
Are F-class cells more tumor-like than IPSC and ES cells given that the F-class cells require continued reprogramming factor expression? If so, would F-class cells pose a higher risk from a clinical perspective?
I’m most excited about the concept that there can potentially be many different kinds of reprogrammed states and pluripotent states. With the arrival of F-class cells on the scene along with IPSC and ES cells, whose to say that there aren’t additional types of pluripotent cells with unique properties that might be harnessed clinically such as G-class, H-class, and so forth?
It seems that as time goes by since the discovery of IPSCs and flexible cell types we scientists need to be more flexible in our thinking as well.