CD15, CD24, and CD29 define a surface biomarker code for neural lineage differentiation of stem cells.

Abstract

Identification and use of cell surface cluster of differentiation (CD) biomarkers have enabled much scientific and clinical progress. We identify a CD surface antigen code for the neural lineage based on combinatorial flow cytometric analysis of three distinct populations derived from human embryonic stem cells: (1) CD15(+)/CD29(HI)/CD24(LO) surface antigen expression defined neural stem cells; (2) CD15(-)/CD29(HI)/CD24(LO) revealed neural crest-like and mesenchymal phenotypes; and (3) CD15(-)/CD29(LO)/CD24(HI) selected neuroblasts and neurons. Fluorescence-activated cell sorting (FACS) for the CD15(-)/CD29(LO)/CD24(HI) profile reduced proliferative cell types in human embryonic stem cell differentiation. This eliminated tumor formation in vivo, resulting in pure neuronal grafts. In conclusion, combinatorial CD15/CD24/CD29 marker profiles define neural lineage development of neural stem cell, neural crest, and neuronal populations from human stem cells. We believe this set of biomarkers enables analysis and selection of neural cell types for developmental studies and pharmacological and therapeutic applications.