NYSCF Collaboration Discovers New Role for Metabolism in Pluripotency

The Context: What makes stem cells special is their ability to turn into other cell types in the body (a characteristic called “pluripotency”). Our understanding of how different molecular pathways control pluripotency, however, is incomplete, and to create stem cell models of disease, we need to identify the most effective ways to induce and maintain pluripotency in the lab.

The Study: Researchers from Memorial Sloan Kettering Cancer Center in collaboration with NYSCF Research Institute scientists discovered that growing stem cells in a culture medium that lacks fat molecules (also known as lipids) helps cells acquire a better state of pluripotency.

The Importance: This study sheds light on the molecular drivers of pluripotency and identifies a new mechanism that converts stem cells to a more stable and improved pluripotent state. A better understanding of what determines pluripotency will allow scientists to create better stem cell models of disease—helping us understand its root causes and develop new treatments.

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Stem cells are unique because they can turn into all cell types of the body — allowing us to study how these different cell types develop and function (both in healthy individuals and in disease). A cell’s ability to turn into other cell types is referred to as “pluripotency,” and while we can manipulate cells into becoming pluripotent in the lab, pluripotency is in part an unstable and not fully understood cell state. Thus, inducing and maintaining pluripotency is a complex and often difficult process.

A major factor that influences the quality of pluripotent stem cells is the culture medium in which scientists grow the cells. Finding the best possible recipe for making an effective cell medium is critical for optimizing stem cell production and downstream processes such as generation of tissue-specific cell types. Current options can be problematic, as the factors controlling pluripotency are not completely elucidated.

A new study in Cell Stem Cell from scientists at Memorial Sloan Kettering Cancer Center in collaboration with the NYSCF Research Institute’s Drs. Scott Noggle and Daniel Paull finds that culturing stem cells in a growth medium (Essential 8^TM) which lacks lipids, improves their pluripotency features, bringing them closer to the “naïve” state of mouse stem cells.

While we know that pluripotent cells often show activated lipid metabolism, the exact role of lipids in pluripotency was previously unclear. The team first observed that growing stem cells in the minimally formulated Essential 8 medium changed the cells’ features to partially resemble those of the mouse “naïve” state. In a series of experiments and computational analyses, they determined that the underlying mechanism driving this conversion was the fat-free nature of Essential 8. The scientists also found that deprivation of stem cells from external lipids helps them enhance their pluripotency by potentially mimicking a natural process that takes place during embryonic development.

With a better understanding of how lipids contribute to pluripotency and a medium that helps cells maintain it, scientists will have an easier time generating induced pluripotent stem cells in the lab. And by integrating this knowledge into large-scale stem cell production platforms such as the NYSCF Global Stem Cell Array ®, researchers will significantly improve their ability to generate high-quality cells and use them to create models of disease and find new treatments.

Original journal article:

Lipid Deprivation Induces a Stable, Naive-to-Primed Intermediate State of Pluripotency in Human PSCs
Cornacchia et al., 2019, Cell Stem Cell 25, 1-17 July 3, 2019. https://doi.org/10.1016/j.stem.2019.05.001