Concise Review: Cell Surface N-Linked Glycoproteins as Potential Stem Cell Markers and Drug Targets

Abstract

Stem cells and their derivatives hold great promise to advance regenerative medicine. Critical to the progression of this field is the identification and utilization of antibody‐accessible cell‐surface proteins for immunophenotyping and cell sorting—techniques essential for assessment and isolation of defined cell populations with known functional and therapeutic properties. Beyond their utility for cell identification and selection, cell‐surface proteins are also major targets for pharmacological intervention. Although comprehensive cell‐surface protein maps are highly valuable, they have been difficult to define until recently. In this review, we discuss the application of a contemporary targeted chemoproteomic‐based technique for defining the cell‐surface proteomes of stem and progenitor cells. In applying this approach to pluripotent stem cells (PSCs), these studies have improved the biological understanding of these cells, led to the enhanced use and development of antibodies suitable for immunophenotyping and sorting, and contributed to the repurposing of existing drugs without the need for high‐throughput screening. The utility of this latter approach was first demonstrated with human PSCs (hPSCs) through the identification of small molecules that are selectively toxic to hPSCs and have the potential for eliminating confounding and tumorigenic cells in hPSC‐derived progeny destined for research and transplantation. Overall, the cutting‐edge technologies reviewed here will accelerate the development of novel cell‐surface protein targets for immunophenotyping, new reagents to improve the isolation of therapeutically qualified cells, and pharmacological studies to advance the treatment of intractable diseases amenable to cell‐replacement therapies.