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SSEA3 and Sialyl Lewis a Glycan Expression Is Controlled by B3GALT5 LTR through Lamin A-NFYA and SIRT1-STAT3 Signaling in Human ES Cells

1
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
2
Department of Biology and Anatomy, National Defense Medical Center, Taipei 11490, Taiwan
3
Department of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
4
Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 177; https://doi.org/10.3390/cells9010177
Received: 25 December 2019 / Revised: 8 January 2020 / Accepted: 8 January 2020 / Published: 10 January 2020
(This article belongs to the Section Stem Cells)
B3GALT5 is involved in the synthesis of embryonic stem (ES) cell marker glycan, stage-specific embryonic antigen-3 (SSEA3). This gene has three native promoters and an integrated retroviral long terminal repeat (LTR) promoter. We found that B3GALT5-LTR is expressed at high levels in human ES cells. B3GALT5-LTR is also involved in the synthesis of the cancer-associated glycan, sialyl Lewis a. Sialyl Lewis a is expressed in ES cells and its expression decreases upon differentiation. Retinoic acid induced differentiation of ES cells, decreased the short form of NFYA (NFYAs), increased phosphorylation of STAT3, and decreased B3GALT5-LTR expression. NFYAs activated, and constitutively-active STAT3 (STAT3C) repressed B3GALT5-LTR promoter. The NFYAs and STAT3C effects were eliminated when their binding sites were deleted. Retinoic acid decreased the binding of NFYA to B3GALT5-LTR promoter and increased phospho-STAT3 binding. Lamin A repressed NFYAs and SSEA3 expression. SSEA3 repression mediated by a SIRT1 inhibitor was reversed by a STAT3 inhibitor. Repression of SSEA3 and sialyl Lewis a synthesis mediated by retinoic acid was partially reversed by lamin A short interfering RNA (siRNA) and a STAT3 inhibitor. In conclusion, B3GALT5-LTR is regulated by lamin A-NFYA and SIRT1-STAT3 signaling that regulates SSEA3 and sialyl Lewis a synthesis in ES cells, and sialyl Lewis a is also a ES cell marker. View Full-Text
Keywords: SSEA3; sialyl Lewis a; embryonic stem cell; differentiation; NFYA; STAT3 SSEA3; sialyl Lewis a; embryonic stem cell; differentiation; NFYA; STAT3
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MDPI and ACS Style

Cai, B.-H.; Lee, H.-Y.; Chou, C.-K.; Wu, P.-H.; Huang, H.-C.; Chao, C.-C.; Chung, H.-Y.; Kannagi, R. SSEA3 and Sialyl Lewis a Glycan Expression Is Controlled by B3GALT5 LTR through Lamin A-NFYA and SIRT1-STAT3 Signaling in Human ES Cells. Cells 2020, 9, 177.

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