ArticleNature structural & molecular biology2021
Retinoic acid signaling is critical during the totipotency window in early mammalian development.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Revisiting retinoic acid in AML therapy: mechanisms of action and rational combination strategies.British journal of cancer · 2026Review
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Generation of eight-cell embryo-like cells from human pluripotent stem cells.Nature protocols · 2026Review
- Phase separation of DUX family proteins drives totipotent-like state via 3D genome reorganization and retrotransposon activation.Protein & cell · 2026Article
- High-throughput functional characterization of enhancers in totipotent-like cells.Nature communications · 2026Article
- A single small molecule-based human embryo model reveals V-ATPase requirement in mammalian blastocyst cavitation.Cell research · 2026Article
- Anti-asthma drug montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling.Signal transduction and targeted therapy · 2026Article
- Retinoic Acid Receptor γ Activity Plays a Critical Role in Regulating Early Mouse Gastruloid Development.International journal of molecular sciences · 2026Article
- Challenges of studying signaling metabolites in early development.Nature structural & molecular biology · 2026Article
- Topologically associating domains define the 3D genome architecture of mouse totipotent-like stem cells.The Journal of biological chemistry · 2026Article
- Coordinated repression of totipotency-associated gene loci by histone methyltransferase EHMT2 via LINE1 regulatory elements.EMBO reports · 2026Article
- A continuous totipotent-like cell-based embryo model recapitulates mouse embryogenesis from zygotic genome activation to gastrulation.Nature cell biology · 2025Article
- Inhibition of Retinoic Acid Receptor Gamma Improves Bovine Embryo Development.Veterinary sciences · 2025Article
- Transgene-free mouse embryo models from chemical reprogramming reach early organogenesis.Cell regeneration (London, England) · 2025Article
- Ints7 deficiency activates DNA damage response to elicit resurgence of endogenous retrovirus MERVL and anastasis of embryonic stem cells.Nucleic acids research · 2025Article
- Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation.Nature reviews. Molecular cell biology · 2025Article
- A taste of one's own medicine:Frontiers in immunology · 2025Article
- Early retinoic acid signaling organizes the body axis and defines domains for the forelimb and eye.Current topics in developmental biology · 2025Review
- Zscan4 mediates ubiquitination and degradation of the corepressor complex to promote chromatin accessibility in 2C-like cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The impact of retrotransposons on zygotic genome activation and the chromatin landscape of early embryos.Annals of the New York Academy of Sciences · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.