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Publication : Genetic analysis of the role of the reprogramming gene LIN-28 in human embryonic stem cells.

First Author  Darr H Year  2009
Journal  Stem Cells Volume  27
Issue  2 Pages  352-62
PubMed ID  19038789 Mgi Jnum  J:148821
Mgi Id  MGI:3846522 Doi  10.1634/stemcells.2008-0720
Citation  Darr H, et al. (2009) Genetic analysis of the role of the reprogramming gene LIN-28 in human embryonic stem cells. Stem Cells 27(2):352-62
abstractText  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.
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