Retinoic acid signaling is critical during the totipotency window in early mammalian development.

Acitretin / pharmacology Animals Blastocyst Inner Cell Mass / cytology Cell Differentiation Cells, Cultured Dose-Response Relationship, Drug Embryonic Stem Cells / cytology Female Gene Expression Regulation, Developmental Gene Regulatory Networks / genetics Genes, Reporter Isotretinoin / pharmacology Male Mice / embryology Mice, Inbred C57BL Mice, Inbred CBA Piperazines / pharmacology Pyrazoles / pharmacology RNA Interference RNA, Messenger / biosynthesis RNA, Small Interfering / pharmacology RNA-Seq Receptors, Retinoic Acid / antagonists & inhibitors Signal Transduction / drug effects Totipotent Stem Cells / cytology Transcription, Genetic Tretinoin / antagonists & inhibitors Retinoic Acid Receptor gamma

Journal

Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374

Informations de publication

Date de publication:
06 2021
Historique:
received: 05 06 2020
accepted: 07 04 2021
pubmed: 29 5 2021
medline: 25 8 2021
entrez: 28 5 2021
Statut: ppublish

Résumé

Totipotent cells hold enormous potential for regenerative medicine. Thus, the development of cellular models recapitulating totipotent-like features is of paramount importance. Cells resembling the totipotent cells of early embryos arise spontaneously in mouse embryonic stem (ES) cell cultures. Such '2-cell-like-cells' (2CLCs) recapitulate 2-cell-stage features and display expanded cell potential. Here, we used 2CLCs to perform a small-molecule screen to identify new pathways regulating the 2-cell-stage program. We identified retinoids as robust inducers of 2CLCs and the retinoic acid (RA)-signaling pathway as a key component of the regulatory circuitry of totipotent cells in embryos. Using single-cell RNA-seq, we reveal the transcriptional dynamics of 2CLC reprogramming and show that ES cells undergo distinct cellular trajectories in response to RA. Importantly, endogenous RA activity in early embryos is essential for zygotic genome activation and developmental progression. Overall, our data shed light on the gene regulatory networks controlling cellular plasticity and the totipotency program.

Identifiants

DOI: 10.1038/s41594-021-00590-w PMID: 34045724 PMC: PMC8195742
pubmed: 34045724
doi: 10.1038/s41594-021-00590-w
pii: 10.1038/s41594-021-00590-w
pmc: PMC8195742
doi:

Substances chimiques

LY2955303 0
Piperazines 0
Pyrazoles 0
RNA, Messenger 0
RNA, Small Interfering 0
Receptors, Retinoic Acid 0
retinoic acid binding protein I, cellular 0
Tretinoin 5688UTC01R
Isotretinoin EH28UP18IF
Acitretin LCH760E9T7

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

521-532

Commentaires et corrections

Type : ErratumIn

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Auteurs

Ane Iturbide (A)

Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany.

Mayra L Ruiz Tejada Segura (ML)

Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany.
Institute of Functional Epigenetics (IFE), Helmholtz Zentrum München, Neuherberg, Germany.
Institute of Computational Biology (ICB), Helmholtz Zentrum München, Neuherberg, Germany.
ORCID: 0000-0003-4217-4458

Camille Noll (C)

Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany.

Kenji Schorpp (K)

Assay Development & Screening Platform, Institute of Molecular Toxicology & Pharmacology (TOXI), Helmholtz Zentrum München, Neuherberg, Germany.

Ina Rothenaigner (I)

Assay Development & Screening Platform, Institute of Molecular Toxicology & Pharmacology (TOXI), Helmholtz Zentrum München, Neuherberg, Germany.

Elias R Ruiz-Morales (ER)

Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany.
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
ORCID: 0000-0002-5801-6190

Gabriele Lubatti (G)

Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany.
Institute of Functional Epigenetics (IFE), Helmholtz Zentrum München, Neuherberg, Germany.
Institute of Computational Biology (ICB), Helmholtz Zentrum München, Neuherberg, Germany.

Ahmed Agami (A)

Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany.
ORCID: 0000-0002-1200-7555

Kamyar Hadian (K)

Assay Development & Screening Platform, Institute of Molecular Toxicology & Pharmacology (TOXI), Helmholtz Zentrum München, Neuherberg, Germany.
ORCID: 0000-0001-8727-2575

Antonio Scialdone (A)

Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany.
Institute of Functional Epigenetics (IFE), Helmholtz Zentrum München, Neuherberg, Germany.
Institute of Computational Biology (ICB), Helmholtz Zentrum München, Neuherberg, Germany.
ORCID: 0000-0002-4956-2843

Maria-Elena Torres-Padilla (ME)

Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany. torres-padilla@helmholtz-muenchen.de.
Faculty of Biology, Ludwig-Maximilians Universität, Munich, Germany. torres-padilla@helmholtz-muenchen.de.
ORCID: 0000-0002-1020-2074

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Pigments biologiques › Caroténoïdes › Rétinoïdes › Acitrétine › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Eucaryotes › Animaux › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Structures de l'embryon › Embryon de mammifère › Blastocyste › Cellules de la masse interne du blastocyste › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Cellules › Cellules cultivées › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes toxicologiques › Relation dose-effet des médicaments › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches embryonnaires › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes au cours du développement › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Séquences d'acides nucléiques régulatrices › Réseaux de régulation génique › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes rapporteurs › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Facteurs biologiques › Pigments biologiques › Caroténoïdes › Rétinoïdes › Isotrétinoïne › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée CBA › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pipérazines › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Pyrazoles › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Interférence par ARN › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Petit ARN interférent › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › RNA-Seq › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs à l'acide rétinoïque › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches totipotentes › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Transcription génétique › Retinoic acid signaling is critical during the...
questionsmedicales.fr › Facteurs biologiques › Pigments biologiques › Caroténoïdes › Rétinoïdes › Trétinoïne › Retinoic acid signaling is critical during the...