Stem Cell Epigenetics, Genomics, and Proteomics

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Human CMP-N-Acetylneuraminic Acid Hydroxylase Is a Novel Stem Cell Marker Linked to Stem Cell-Specific Mechanisms†‡§

  1. Johanna Nystedt1,¶,*,
  2. Heidi Anderson1,
  3. Tia Hirvonen1,
  4. Ulla Impola1,
  5. Taina Jaatinen1,
  6. Annamari Heiskanen2,
  7. Maria Blomqvist2,
  8. Tero Satomaa2,
  9. Jari Natunen2,
  10. Juhani Saarinen2,
  11. Petri Lehenkari3,
  12. Leena Valmu1,
  13. Jarmo Laine1

Article first published online: 4 NOV 2009

DOI: 10.1002/stem.250

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 2, pages 258–267, February 2010

Additional Information

How to Cite

Nystedt, J., Anderson, H., Hirvonen, T., Impola, U., Jaatinen, T., Heiskanen, A., Blomqvist, M., Satomaa, T., Natunen, J., Saarinen, J., Lehenkari, P., Valmu, L. and Laine, J. (2010), Human CMP-N-Acetylneuraminic Acid Hydroxylase Is a Novel Stem Cell Marker Linked to Stem Cell-Specific Mechanisms. STEM CELLS, 28: 258–267. doi: 10.1002/stem.250

Author Information

  1. 1

    Research and Development, Finnish Red Cross Blood Service, Helsinki, Finland

  2. 2

    Glykos Finland Ltd., Helsinki, Finland

  3. 3

    Department of Anatomy and Clinical Research Center, University of Oulu, Oulu, Finland

  1. Telephone: +358-44-3296491; Fax: +358-9-5801 1310

*Finnish Red Cross Blood Service, Kivihaantie 7, FIN-00310 Helsinki, Finland

  1. †

    Author contributions: J. Nystedt: Conception and design, collection and/or assembly of data (main contributor), data analysis and interpretation (main contributor), manuscript writing (main contributor), final approval of manuscript; H.A.: Conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; T.H., U.I., M.B., T.S.: Collection and/or assembly of data, data analysis and interpretation, final approval of manuscript; T.J.: Conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, final approval of manuscript; A.H.: Data analysis and interpretation, manuscript writing, final approval of manuscript; J. Natunen: Conception and design, data analysis and interpretation, final approval of manuscript; J.S.: Conception and design, financial support, data analysis and interpretation, final approval of manuscript; P.L.: Provision of study material or patients, final approval of manuscript; L.V.: Administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript; J.L.: Conception and design, financial support, administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSEXPRESS January 28, 2010.

Publication History

  1. Issue published online: 16 FEB 2010
  2. Article first published online: 4 NOV 2009
  3. Accepted manuscript online: 4 NOV 2009 12:00AM EST
  4. Manuscript Accepted: 27 OCT 2009
  5. Manuscript Received: 24 JUN 2009

Funded by

  • National Technology Agency of Finland

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Keywords:

  • CMP-N-acetylneuraminic acid hydroxylase;
  • Neu5Gc;
  • Xenoantigen;
  • N-glycolylneuraminic acid;
  • Stem cells;
  • Wnt

Abstract

Human stem cells contain substantial amounts of the xenoantigen N-glycolylneuraminic acid (Neu5Gc), although the levels of Neu5Gc are low or undetectable in human body fluids and most other human tissues. The lack of Neu5Gc in human tissues has been previously explained by the loss of hydroxylase activity of the human CMP-N-acetylneuraminic acid hydroxylase (CMAH) protein caused by a genetic error in the human Cmah gene. We thus wanted to investigate whether the human redundant Cmah gene could still function in stem cell-specific processes. In this study, we show that CMAH gene expression is significantly upregulated in the adult stem cell populations studied, both of hematopoietic and mesenchymal origin, and identify CMAH as a novel stem cell marker. The CMAH content co-occurs with higher levels of Neu5Gc within stem cells as measured by mass spectrometric profiling. It seems that despite being enzymatically inactive, human CMAH may upregulate the Neu5Gc content of cells by enhancing Neu5Gc uptake from exogenous sources. Furthermore, exposure to exogenous Neu5Gc caused rapid phosphorylation of β-catenin in both CMAH overexpressing cells and bone marrow-derived mesenchymal stem cells, thereby inactivating Wnt/β-catenin signaling. The data demonstrate the first molecular evidence for xenoantigen Neu5Gc-induced alteration of crucial stem cell-specific signaling systems for the maintenance of self renewal. These results add further emphasis to the crucial need for completely xenofree culturing conditions for human stem cells. STEM CELLS 2010;28:258–267

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