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

Henia Dark, Nissim Benvenisty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)352-362
Number of pages11
JournalStem Cells
Volume27
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • Cell differentiation
  • Embryonic stem cells
  • LIN-28 protein

Fingerprint

Dive into the research topics of 'Genetic analysis of the role of the reprogramming gene LIN-28 in human embryonic stem cells'. Together they form a unique fingerprint.

Cite this