Activation of retinoic acid receptor signaling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies

Zoltan Simandi; Balint Laszlo Balint; Szilard Poliska; Ralph Ruhl; Laszlo Nagy

doi:10.1016/j.febslet.2010.05.052

Activation of retinoic acid receptor signaling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies

Zoltan Simandi, Balint Laszlo Balint, Szilard Poliska, Ralph Ruhl, Laszlo Nagy

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Retinoid signaling has been implicated in embryonic stem cell differentiation. Here we present a systematic analysis of gene expression changes in mouse embryonic stem cells (mESCs), during their spontaneous differentiation into embryoid bodies and the effect of all-trans retinoic acid (ATRA) on this process. We show that retinoic acid is present in the serum and is sufficient to activate retinoid signaling at a basal level in undifferentiated mESCs. This signal disappears during embryoid body formation. However exogenously added ATRA resets the spontaneous differentiation programs in embryoid bodies and initiates a distinct genetic program. These data suggest that retinoid signaling not only promotes a particular pathway but also acts as a context dependent general coordinator of the differentiation states in embryonic stem cells.

Original language	English (US)
Pages (from-to)	3123-3130
Number of pages	8
Journal	FEBS Letters
Volume	584
Issue number	14
DOIs	https://doi.org/10.1016/j.febslet.2010.05.052
State	Published - Jul 2010
Externally published	Yes

Keywords

All-trans retinoic acid
Embryoid body
Mouse embryonic stem cell
Retinoic acid receptor
Retinoid signaling
Transcription

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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title = "Activation of retinoic acid receptor signaling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies",

abstract = "Retinoid signaling has been implicated in embryonic stem cell differentiation. Here we present a systematic analysis of gene expression changes in mouse embryonic stem cells (mESCs), during their spontaneous differentiation into embryoid bodies and the effect of all-trans retinoic acid (ATRA) on this process. We show that retinoic acid is present in the serum and is sufficient to activate retinoid signaling at a basal level in undifferentiated mESCs. This signal disappears during embryoid body formation. However exogenously added ATRA resets the spontaneous differentiation programs in embryoid bodies and initiates a distinct genetic program. These data suggest that retinoid signaling not only promotes a particular pathway but also acts as a context dependent general coordinator of the differentiation states in embryonic stem cells.",

keywords = "All-trans retinoic acid, Embryoid body, Mouse embryonic stem cell, Retinoic acid receptor, Retinoid signaling, Transcription",

author = "Zoltan Simandi and Balint, {Balint Laszlo} and Szilard Poliska and Ralph Ruhl and Laszlo Nagy",

note = "Funding Information: We thank Ibolya Furtos for technical assistance and members of the Nagy laboratory for comments on the manuscript. L.N. is an International Scholar of HHMI and holds a Wellcome Trust Senior Research Fellowship in Biomedical Sciences and also supported by grants from the Hungarian Scientific Research Fund ( OTKA NK72730 ) and TAMOP-4.2.2/08/1 . Z.S. is the recipient of a Richter Gedeon PhD Fellowship. This work was also supported by a grant from the Hungarian Science Research Fund (OTKA F68254 to B.L.B.), B.L.B. is a recipient of the Bolyai Fellowship of the Hungarian Academy of Sciences. ",

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AU - Nagy, Laszlo

N1 - Funding Information: We thank Ibolya Furtos for technical assistance and members of the Nagy laboratory for comments on the manuscript. L.N. is an International Scholar of HHMI and holds a Wellcome Trust Senior Research Fellowship in Biomedical Sciences and also supported by grants from the Hungarian Scientific Research Fund ( OTKA NK72730 ) and TAMOP-4.2.2/08/1 . Z.S. is the recipient of a Richter Gedeon PhD Fellowship. This work was also supported by a grant from the Hungarian Science Research Fund (OTKA F68254 to B.L.B.), B.L.B. is a recipient of the Bolyai Fellowship of the Hungarian Academy of Sciences.

PY - 2010/7

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N2 - Retinoid signaling has been implicated in embryonic stem cell differentiation. Here we present a systematic analysis of gene expression changes in mouse embryonic stem cells (mESCs), during their spontaneous differentiation into embryoid bodies and the effect of all-trans retinoic acid (ATRA) on this process. We show that retinoic acid is present in the serum and is sufficient to activate retinoid signaling at a basal level in undifferentiated mESCs. This signal disappears during embryoid body formation. However exogenously added ATRA resets the spontaneous differentiation programs in embryoid bodies and initiates a distinct genetic program. These data suggest that retinoid signaling not only promotes a particular pathway but also acts as a context dependent general coordinator of the differentiation states in embryonic stem cells.

AB - Retinoid signaling has been implicated in embryonic stem cell differentiation. Here we present a systematic analysis of gene expression changes in mouse embryonic stem cells (mESCs), during their spontaneous differentiation into embryoid bodies and the effect of all-trans retinoic acid (ATRA) on this process. We show that retinoic acid is present in the serum and is sufficient to activate retinoid signaling at a basal level in undifferentiated mESCs. This signal disappears during embryoid body formation. However exogenously added ATRA resets the spontaneous differentiation programs in embryoid bodies and initiates a distinct genetic program. These data suggest that retinoid signaling not only promotes a particular pathway but also acts as a context dependent general coordinator of the differentiation states in embryonic stem cells.

KW - All-trans retinoic acid

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KW - Retinoic acid receptor

KW - Retinoid signaling

KW - Transcription

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Activation of retinoic acid receptor signaling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies

Abstract

Keywords

ASJC Scopus subject areas

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