L1 cell adhesion molecule, a novel surface molecule of human embryonic stem cells, is essential for self-renewal and pluripotency

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Title
L1 cell adhesion molecule, a novel surface molecule of human embryonic stem cells, is essential for self-renewal and pluripotency
Author(s)
Yeon Sung Son; R H Seong; C J Ryu; Yee Sook ChoKwang-Hee Bae; Sang Jeon Chung; B Lee; Jeong Ki Min; H J Hong
Bibliographic Citation
Stem Cells, vol. 29, no. 12, pp. 2094-2099
Publication Year
2011
Abstract
Despite the recent identification of surface markers of undifferentiated human embryonic stem cells (hESCs), the crucial cell-surface molecules that regulate the self-renewal capacity of hESCs remain largely undefined. Here, we generated monoclonal antibodies (MAbs) that specifically bind to undifferentiated hESCs but not to mouse embryonic stem cells. Among these antibodies, we selected a novel MAb, 4-63, and identified its target antigen as the L1 cell adhesion molecule (L1CAM) isoform 2. Notably, L1CAM expressed in hESCs lacked the neuron-specific YEGHH and RSLE peptides encoded by exons 2 and 27, respectively. L1CAM colocalized with hESC-specific cell-surface markers, and its expression was markedly downregulated on differentiation. Stable L1CAM depletion markedly decreased hESC proliferation, whereas L1CAM overexpression increased proliferation. In addition, the expression of octamer-binding transcription factor 4, Nanog, sex-determining region Y-box 2, and stage-specific embryonic antigen (SSEA)-3 was markedly downregulated, whereas lineage-specific markers and SSEA-1 were upregulated in L1CAM-depleted hESCs. Interestingly, the actions of L1CAM in regulating the proliferation and differentiation of hESCs were exerted predominantly through the fibroblast growth factor receptor 1 signaling pathway. Taken together, our results suggest that L1CAM is a novel cell-surface molecule that plays an important role in the maintenance of self-renewal and pluripotency in hESCs.
Keyword
Cell-surface markerFibroblast growth factor receptor 1Human embryonic stem cellsL1 cell adhesion moleculeMonoclonal antibody
ISSN
1066-5099
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/stem.754
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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