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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 2 FEB 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 2, pages 352–362, February 2009
How to Cite
Darr, H. and Benvenisty, N. (2009), Genetic Analysis of the Role of the Reprogramming Gene LIN-28 in Human Embryonic Stem Cells. STEM CELLS, 27: 352–362. doi: 10.1634/stemcells.2008-0720
Author contributions: H.D.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; N.B.: conception and design, data analysis and interpretation, manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSExpress November 26, 2008.
- Issue published online: 2 FEB 2009
- Article first published online: 2 FEB 2009
- Manuscript Accepted: 12 NOV 2008
- Manuscript Received: 25 JUL 2008
- “Bereshit Consortium” The Israeli Ministry of Trade and Industry. Grant Number: 37675
- European Community (ESTOOLS). Grant Number: 018739
- Legacy fund
Vol. 33, Issue 7, 2360, Article first published online: 19 JUN 2015
- Embryonic stem cells;
- Cell differentiation;
- LIN-28 protein
LIN-28 is a gene recently shown to be involved in the conversion of somatic cells to induced pluripotent stem cells. We have previously shown that LIN-28 is highly expressed in human embryonic stem cells (HESCs); however, its role in these cells has not been investigated. We now show that, like OCT4, SOX2, and NANOG, LIN-28 is downregulated during differentiation of HESCs into embryoid bodies. In addition, we investigate the role of LIN-28 in HESCs by manipulation of its expression levels. LIN-28 overexpression impairs the ability of cells to grow at clonal densities, due to increased differentiation and decreased cell division. Analysis of cell differentiation under these conditions revealed that it is mostly towards the extraembryonic endoderm lineage. Moreover, we show that, during early mouse development, high levels of Lin-28 are also observed in the extraembryonic endoderm, and therefore it seems that, both in vitro and in vivo, high levels of LIN-28 may specify an extraembryonic endoderm fate. However, LIN-28 seems dispensable for self-renewal of HESCs; its downregulation neither impairs HESC proliferation nor leads to their differentiation. Thus, LIN-28 does not seem to be involved in the self-renewal of HESCs, but rather seems to be involved in their decision to switch from self-renewal to differentiation. STEM CELLS2009;27:352–362