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EMBRYONIC STEM CELLS

Pleiotrophin Enhances Clonal Growth and Long-Term Expansion of Human Embryonic Stem Cells

^aStem Cell and Developmental Biology, Genome Institute of Singapore, Singapore;
^bDepartment of Chemical Engineering and Chemical Technology, Faculty of Engineering, South Kensington Campus, Imperial College London, United Kingdom;
^cBioinformatics Institute, Singapore;
^dCambridge Institute for Medical Research, Wellcome Trust, Addenbrookes Hospital, Cambridge, United Kingdom;
^eLaboratory of Stem Cell Biology, Singapore Stem Cell Consortium, Singapore;
^fDepartment of Medicine, National University of Singapore, Singapore;
^gStem Cells and Regenerative Medicine, Invitrogen Corp., Carlsbad, California, USA;
^hHarvard Institutes of Medicine, Harvard Medical School, Boston, Massachusetts, USA

Key Words. Transcriptome database • Feeder cells and human embryonic stem cells • Growth factors and receptors Clonal efficiency and embryonic stem expansion

Correspondence: Bing Lim, M.D., Ph.D., Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore, 138672. Telephone: 65-6478-8156; Fax: 65-6478-9005; e-mail: limb1{at}gis.a-star.edu.sg; Mahendra Rao, M.D., Ph.D., Stem Cells and Regenerative Medicine, Invitrogen Corp., 5781 Van Allen Way, Carlsbad, California 92008, USA. Telephone: 240-379-4119; Fax: 410-510-1188; e-mail: vzeq2tcr{at}verizon.net

Received May 15, 2007; accepted for publication August 23, 2007.
First published online in STEM CELLS EXPRESS   September 6, 2007.



To identify additional growth factors for optimizing propagation of human embryonic stem cells (hESCs), we mined publicly available data sets for the transcriptomes of murine and human ESCs and feeder cells, thereby generating a list of growth factors and complementary receptors. We identified the major pathways previously reported to be important, as well as several new ones. One pathway is the Pleiotrophin (PTN)-Pleiotrophin receptor (PTPRZ1) axis. Murine fibroblasts secrete Ptn, whereas hESCs expressed PTPRZ1, which is downregulated upon differentiation. Depletion of PTPRZ1 resulted in decreased colony formation and lower recovery of hESCs. Supplementation of chemically defined medium for feeder-free propagation of hESCs with PTN allowed higher recovery of hESCs without loss of pluripotency. PTN-PTPRZ1 functions here predominantly via an antiapoptotic effect mediated in part by the activation of Akt. These findings reveal the underlying importance of PTN in hESC survival and its usefulness in the clonal manipulation and large-scale propagation of hESCs.

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

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