Logo Logo
Switch Language to German

Iturbide, Ane; Segura, Mayra L. Ruiz Tejeda; Noll, Camille; Schorpp, Kenji; Rothenaigner, Ina; Ruiz-Morales, Elias R.; Lubatti, Gabriele; Agami, Ahmed; Hadian, Kamyar; Scialdone, Antonio and Torres-Padilla, Maria-Elena (2021): Retinoic acid signaling is critical during the totipotency window in early mammalian development. In: Nature Structural & Molecular Biology, Vol. 28, No. 6: 521-

Full text not available from 'Open Access LMU'.


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. High-throughput chemical screening identifies retinoic acid signaling as a regulatory pathway of 2-cell-like cell reprogramming and early mouse development.

Actions (login required)

View Item View Item