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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 16 NOV 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 12, pages 1952–1962, December 2011
How to Cite
Alva, J. A., Lee, G. E., Escobar, E. E. and Pyle, A. D. (2011), Phosphatase and Tensin Homolog Regulates the Pluripotent State and Lineage Fate Choice in Human Embryonic Stem Cells. STEM CELLS, 29: 1952–1962. doi: 10.1002/stem.748
Author contributions: J.A.A. and G.E.L.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; E.E.E.: collection and/or assembly of data; A.D.P.: conception and design, financial support, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS September 21, 2011.
- Issue published online: 16 NOV 2011
- Article first published online: 16 NOV 2011
- Accepted manuscript online: 21 SEP 2011 01:15PM EST
- Manuscript Accepted: 13 SEP 2011
- Manuscript Received: 5 APR 2011
- UCLA Jonsson Comprehensive Cancer Center (JCCC)
- The Eli & Edythe Broad Center of Regenerative Medicine
- Stem Cell Research at UCLA and the University of California Cancer Research Coordinating Committee (CRCC)
- UCLA Tumor Immunology Training Grant Fellowship. Grant Number: T32CA009120-33
- University of California Regents President's Postdoctoral Fellowship
- Pluripotent stem cells;
- Embryonic stem cells;
- Cell signaling
Understanding the intrinsic and extrinsic signals that regulate the molecular basis of the pluripotent state may improve our understanding of mammalian embryogenesis, different states of pluripotency, and our ability to tailor lineage differentiation. Although the role of the PI3K/Akt pathway in the self-renewal and maintenance of mESCs is well-established, the specific contribution of the pathway or of its negative regulator, PTEN, in the maintenance of the human pluripotent state is less understood. To explore the PI3K/AKT pathway in human embryonic stem cell (hESC) pluripotency and differentiation, we generated stable PTEN knockdown (KD) hESCs using short hairpin RNA. Similar to mESCs, we found that PTEN KD hESCs have increased self-renewal, cell survival, and proliferation over multiple passages compared to control cells. However, in contrast to mESCs, in vitro, PTEN KD hESCs differentiated inefficiently in directed differentiation assays, in part due to the continued maintenance of OCT4 and NANOG expression. In teratoma assays, PTEN KD hESCs generated tissues from the three germ layers, although with a bias toward neuroectoderm differentiation. These results demonstrate that PTEN is a key regulator of hESC growth and differentiation, and manipulation of this pathway may improve our ability to regulate and understand the pluripotent state. STEM CELLS 2011;29:1952–1962.