Expression of a mutant retinoic acid receptor β alters lineage differentiation in mouse embryonic stem cells

Christina Chatzi, Christina E. Van Den Brink, Paul T. Van Der Saag, Colin D. McCaig, Sanbing Shen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

We have introduced 1 to 2 copies of a deletion mutant (βΔC) of the human retinoic acid receptor β into mouse embryonic stem (ES) cells. The βΔC-expressing cells were 10 to 100 times less sensitive to RA-induced differentiation in comparison with their parental cells. In the presence of 10-7 M RA in monolayer culture, they showed no growth arrest or differentiation, but remained pluripotent. Embryoid bodies (EBs) derived from βΔC-expressing cells differentiated into cardiomyocytes rather than neurons after treatment with 10-6 M RA, and became neurons upon exposure to 10-5 or 10-4 M RA. Remarkably, after 10 passages of continuous culture in the presence of 10-7 M RA, they still were able to form chimeras after injection into blastocysts. These data suggest that appropriate levels of normal retinoid receptors are crucial for lineage-specific differentiation of mouse ES cells in vitro. The βΔC mutant protein may prove to be useful in promoting "stemness" of ES cells in culture.

Original languageEnglish (US)
Pages (from-to)951-960
Number of pages10
JournalStem Cells and Development
Volume19
Issue number7
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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