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

Christina Chatzi, Christina E van den Brink, Paul T van der Saag, Colin Darnley McCaig, Sanbing Shen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We have introduced 1 to 2 copies of a deletion mutant (betaDeltaC) of the human retinoic acid receptor beta into mouse embryonic stem (ES) cells. The betaDeltaC-expressing cells were 10 to 100 times less sensitive to RA-induced differentiation in comparison to 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 betaDeltaC-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 betaDeltaC mutant protein may prove to be useful in promoting "stemness" of ES cells in culture.
Original languageEnglish
Pages (from-to)951-960
Number of pages10
JournalStem Cells and Development
Volume19
Issue number7
DOIs
Publication statusPublished - Jul 2010

Fingerprint

Embryoid Bodies
Neurons
Retinoids
Blastocyst
Mutant Proteins
Embryonic Stem Cells
Cardiac Myocytes
Cell Culture Techniques
Injections
Growth
retinoic acid receptor beta
Mouse Embryonic Stem Cells
N,N-methylethylphenylcarbamate
Therapeutics
In Vitro Techniques

Keywords

  • carcinoma-cells
  • in-vitro
  • binding
  • alpha
  • gene
  • DNA
  • cardiomyocytes
  • derivation
  • selection
  • element

Cite this

Expression of a mutant retinoic acid receptor beta alters lineage differentiation in mouse embryonic stem cells. / Chatzi, Christina; van den Brink, Christina E; van der Saag, Paul T; McCaig, Colin Darnley; Shen, Sanbing.

In: Stem Cells and Development, Vol. 19, No. 7, 07.2010, p. 951-960.

Research output: Contribution to journalArticle

Chatzi, Christina ; van den Brink, Christina E ; van der Saag, Paul T ; McCaig, Colin Darnley ; Shen, Sanbing. / Expression of a mutant retinoic acid receptor beta alters lineage differentiation in mouse embryonic stem cells. In: Stem Cells and Development. 2010 ; Vol. 19, No. 7. pp. 951-960.
@article{83c1147a3a9d45e18ecae968d4d9ae7f,
title = "Expression of a mutant retinoic acid receptor beta alters lineage differentiation in mouse embryonic stem cells",
abstract = "We have introduced 1 to 2 copies of a deletion mutant (betaDeltaC) of the human retinoic acid receptor beta into mouse embryonic stem (ES) cells. The betaDeltaC-expressing cells were 10 to 100 times less sensitive to RA-induced differentiation in comparison to 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 betaDeltaC-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 betaDeltaC mutant protein may prove to be useful in promoting {"}stemness{"} of ES cells in culture.",
keywords = "carcinoma-cells, in-vitro, binding, alpha, gene, DNA, cardiomyocytes, derivation, selection, element",
author = "Christina Chatzi and {van den Brink}, {Christina E} and {van der Saag}, {Paul T} and McCaig, {Colin Darnley} and Sanbing Shen",
year = "2010",
month = "7",
doi = "10.1089/scd.2009.0517",
language = "English",
volume = "19",
pages = "951--960",
journal = "Stem Cells and Development",
issn = "1547-3287",
publisher = "Mary Ann Liebert Inc.",
number = "7",

}

TY - JOUR

T1 - Expression of a mutant retinoic acid receptor beta 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 Darnley

AU - Shen, Sanbing

PY - 2010/7

Y1 - 2010/7

N2 - We have introduced 1 to 2 copies of a deletion mutant (betaDeltaC) of the human retinoic acid receptor beta into mouse embryonic stem (ES) cells. The betaDeltaC-expressing cells were 10 to 100 times less sensitive to RA-induced differentiation in comparison to 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 betaDeltaC-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 betaDeltaC 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 (betaDeltaC) of the human retinoic acid receptor beta into mouse embryonic stem (ES) cells. The betaDeltaC-expressing cells were 10 to 100 times less sensitive to RA-induced differentiation in comparison to 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 betaDeltaC-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 betaDeltaC mutant protein may prove to be useful in promoting "stemness" of ES cells in culture.

KW - carcinoma-cells

KW - in-vitro

KW - binding

KW - alpha

KW - gene

KW - DNA

KW - cardiomyocytes

KW - derivation

KW - selection

KW - element

U2 - 10.1089/scd.2009.0517

DO - 10.1089/scd.2009.0517

M3 - Article

VL - 19

SP - 951

EP - 960

JO - Stem Cells and Development

JF - Stem Cells and Development

SN - 1547-3287

IS - 7

ER -