Discovery of New Stem Cell Class Might Accelerate Research

An international team of scientists has discovered a new class of stem cell. This project consisted of a massive collaboration between over 50 scientists on four continents, that has been affectionately named, “Project Grandiose.” This new class of stem cells, known as a F-class cell, opens new and exciting avenues for generating designer cells that could be safer and more efficiently used in therapy.

Andras Nagy, Ph.D., from the University of Toronto’s Institute of Medical Sciences led this group in conducting a high-resolution characterization of the molecular events that are required for the reprogramming of stem cells. In particular, Nagy and his colleagues were interested in ways to control the path to pluripotency. In this analysis, they discovered an alternative reprogrammed cell, which they called F-class stem cells.

It has been known for many years that when mature, adult cells are reprogrammed into induced pluripotent stem cells (iPSCs) by means forcing expression of key transcription factors (Oct4, Klf4, Sox2, and c-Myc), some cells will stably not express the pluripotency gene Nanog, and fail to acquire full pluripotency, even though these cells look like embryonic stem cells (see Fussner, E. et al. EMBO J. 30, 1778–1789 (2011); Sridharan, R. et al. Cell 136, 364–377 (2009); and Chen, J. et al. Nature Genet. 45, 34–42 (2013)). These partially reprogrammed cells seem to indicate that there are other cell types that can be formed by reprogramming that are not fully pluripotent. Strangely, some labs have reported that treating partially pluripotent cells with vitamin C can reprogram to cells to full pluripotency (Esteban, M. A. et al. Cell Stem Cell 6, 71–79 (2009)).

Nagy and his colleagues used a whole battery of tests to take detailed snapshots of every stage of reprogramming, and in the process, revealed an alternative state of pluripotency. They discovered that high levels of expression of the four reprogramming factors generates cells that do not form typical ESC-like colonies in culture, but are still pluripotent. These are the F-type cells.  F-type cells derived their name from the fuzzy boundaries they form when they grow in culture.

When F-type cells were compared to embryonic-like stem cells, the F-type cells are easier to make, less expensive, and faster to grow. Thus F-class stem cells can be produced more economically in large quantities and this should accelerate drug-screening efforts, disease modeling, and eventually the development of treatments for different illnesses.