Open AccessBone Morphogenetic Protein Promotes Lewis X Stage‐Specific Embryonic Antigen 1 Expression Thereby Interfering with Neural Precursor and Stem Cell Proliferation
Author(s) -
LuqueMolina Inma,
Khatri Priti,
SchmidtEdelkraut Udo,
Simeonova Ina K.,
HölzlWenig Gabriele,
Mandl Claudi,
Ciccolini Francesca
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2701
Subject(s) - biology , embryonic stem cell , microbiology and biotechnology , neural stem cell , stem cell , bone morphogenetic protein , bone morphogenetic protein 4 , immunology , genetics , gene
The glycoprotein Prominin‐1 and the carbohydrate Lewis X stage‐specific embryonic antigen 1 (LeX‐SSEA1) both have been extensively used as cell surface markers to purify neural stem cells (NSCs). While 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 signaling 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 signaling, thereby downregulating the proliferation of subependymal zone precursors including NSCs. S tem C ells 2017;35:2417–2429