Bone morphogenetic protein promotes LeX‐SSEA1 expression thereby interfering with neural precursor and stem cell proliferation

The glycoprotein Prominin-1 and the carbohydrate LeX-SSEA1 both have been extensively used as cell surface markers to purify neural stem cells (NSCs). Whereas Prominin-1 labels a specialized membrane region in NSCs and ependymal cells, the specificity of LeX-SSEA1 expression and its biological significance are still unknown. To address these issues, we have here monitored the expression of the carbohydrate in neonatal and adult NSCs and in their progeny. Our results show that the percentage of immunopositive cells and the levels of LeX-SSEA1 immunoreactivity both increase with postnatal age across all stages of the neural lineage. This is associated with decreased proliferation in precursors including NSCs, which accumulate the carbohydrate at the cell surface while remaining quiescent. Exposure of precursors to bone morphogenetic protein (BMP) increases LEX-SSEA1 expression, which promotes cell cycle withdrawal by a mechanism involving LeX-SSEA1-mediated interaction at the cell surface. Conversely, interference with either BMP signalling or with LeX-SSEA1 promotes proliferation to a similar degree. Thus, in the postnatal germinal niche the expression of LeX-SSEA1 increases with age and exposure to BMP signalling, thereby downregulating the proliferation of SEZ precursors including NSCs. This article is protected by copyright. All rights reserved.