TY - JOUR
T1 - Expression of a mutant retinoic acid receptor β alters lineage differentiation in mouse embryonic stem cells
AU - Chatzi, Christina
AU - Van Den Brink, Christina E.
AU - Van Der Saag, Paul T.
AU - McCaig, Colin D.
AU - Shen, Sanbing
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2010/7/1
Y1 - 2010/7/1
N2 - 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.
AB - 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.
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U2 - 10.1089/scd.2009.0517
DO - 10.1089/scd.2009.0517
M3 - Article
C2 - 20064013
AN - SCOPUS:77954916991
SN - 1547-3287
VL - 19
SP - 951
EP - 960
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 7
ER -