Pleiotrophin enhances clonal growth and long-term expansion of human embryonic stem cells.
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.
Soh
Boon Seng
BS
Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore.
Song
Chun Meng
CM
Vallier
Ludovic
L
Li
Pin
P
Choong
Cleo
C
Yeo
Boon Huat
BH
Lim
Elaine Hsuen
EH
Pedersen
Roger A
RA
Yang
Henry He
HH
Rao
Mahendra
M
Lim
Bing
B
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013995:Time