Mass Spectrometry Imaging Reveals Early Metabolic Priming of Cell Lineage in Differentiating Human-Induced Pluripotent Stem Cells

A new study from Melissa L. Kemp, a researcher at Georgia Institute of Technology and Emory University in Atlanta, Georgia, USA, has used mass spectrometry imaging to reveal the metabolic changes that occur during the differentiation of induced pluripotent stem cells (iPSCs) (1). These findings could help to establish quality control measures during the early stages of differentiation, which is important in regenerative medicine.

Human or animal cells on blue background. Concept Early stage embryo Medicine scientific concept, Stem cell research and treatment. 3D illustration. | Image Credit: © rost9 - stock.adobe.com

iPSCs can be reprogrammed from a patient’s own adult cells and have the potential to be differentiated into any cell type, making them useful in regenerative medicine. However, quality control measures are essential to ensure the safety and potency of these cells during manufacturing. In a clinical setting, quality control can include the confirmation of cellular pluripotency and the quantification of phenotype marker genes, but little is known about the early metabolic changes that occur during differentiation.

iPSCs are cells that are artificially created from somatic cells, such as skin cells or blood cells, by introducing specific genes that reprogram them to return to a stem cell-like state. These cells have the ability to differentiate into various types of cells, including those that make up organs and tissues in the body. iPSCs are being used in research and potential therapies for a wide range of diseases and conditions, as they offer a way to study disease mechanisms and develop personalized treatments. With their potential to revolutionize regenerative medicine, iPSCs have garnered significant attention in the scientific community and are a promising tool for advancing healthcare.

Kemp's study utilized mass spectrometry imaging to investigate changes in iPSC lipid profiles during the initial loss of pluripotency over the course of spontaneous differentiation. The study found that several phosphatidylinositol (PI) species emerged as early metabolic markers of pluripotency loss, preceding changes in the pluripotency transcription factor Oct4. Additionally, the continuous inhibition of phosphatidylethanolamine N-methyltransferase during differentiation resulted in the enhanced maintenance of pluripotency.

The findings of this study could help establish quality control measures during the early stages of differentiation and could also aid in the development of directed differentiation protocols. Lipidomic metrics can be used to predict the early lineage specification in the initial stages of spontaneous iPSC differentiation, providing valuable information for regenerative medicine.

Reference

(1) Nikitina, A. A.; Van Grouw, A.; Roysam, T.; Huang, D.; Fernández, F. M.; Kemp, M. L. Mass Spectrometry Imaging Reveals Early Metabolic Priming of Cell Lineage in Differentiating Human-Induced Pluripotent Stem Cells. Anal. Chem. 2023, 95, 11, 4880–4888. DOI: https://doi.org/10.1021/acs.analchem.2c04416