@article{e6630106d5664d01b61012b620f65472,
title = "Time-aligned hourglass gastrulation models in rabbit and mouse",
abstract = "The hourglass model describes the convergence of species within the same phylum to a similar body plan during development; however, the molecular mechanisms underlying this phenomenon in mammals remain poorly described. Here, we compare rabbit and mouse time-resolved differentiation trajectories to revisit this model at single-cell resolution. We modeled gastrulation dynamics using hundreds of embryos sampled between gestation days 6.0 and 8.5 and compared the species using a framework for time-resolved single-cell differentiation-flows analysis. We find convergence toward similar cell-state compositions at E7.5, supported by the quantitatively conserved expression of 76 transcription factors, despite divergence in surrounding trophoblast and hypoblast signaling. However, we observed noticeable changes in specification timing of some lineages and divergence of primordial germ cell programs, which in the rabbit do not activate mesoderm genes. Comparative analysis of temporal differentiation models provides a basis for studying the evolution of gastrulation dynamics across mammals.",
author = "Yoav Mayshar and Ofir Raz and Saifeng Cheng and Raz Ben-Yair and Ron Hadas and Netta Reines and Markus Mittnenzweig and Oren Ben-Kiki and Aviezer Lifshitz and Amos Tanay and Yonatan Stelzer",
note = "We thank the Tanay and Stelzer group members for discussion and advice. Special thanks to Hernan Rubinstein for help in graphic design and embryo illustrations. Y.S. is the incumbent of the Louis and Ida Rich Career Development Chair and a member of the European Molecular Biology Organization (EMBO) Young Investigator Program. Research in the Stelzer lab is supported by European Research Council (ERC_StG 852865), Human Frontier Science Program (CDA00023/2019-C), Moross Integrated Cancer Center, Helen and Martin Kimmel Stem Cell Institute, the Schwartz/Reisman Collaborative Science Program, and Abisch Frenkel Foundation. This research was also generously supported by Barry and Janet Lang, Hadar Impact Fund, Lord Sieff of Brimpton Memorial Fund, Janet and Steven Anixter, JoAnne Silva, Maurice and Vivienne Wohl Biology Endowment, and Lester and Edward Anixter Family. C.S. was supported by the EMBO long-term fellowship (ALTF 268-2018). M.M. was a postdoctoral fellow of the Minerva Stiftung and is supported by the Walter Benjamin Program of the German Research Foundation (DFG). A.T. is supported by the European Research Council (ERC CoG scAssembly), the EU BRAINTIME project, the Israel Science Foundation, and the Chen-Zuckerberg Foundation. This research was further supported Israeli Council for Higher Education (CHE) Data Science program and by a grant from Madame Olga Klein-Astracha. Author contributions - Y.M., O.R., A.T., and Y.S. conceived and designed the experiment, and performed data analysis and its interpretation. S.C., R.B.-Y., and R.H. assisted in the collection of single cells from individual embryos. N.R. prepared scRNA-seq libraries. A.L., M.M., and O.B.-K. assisted with scRNA-seq data analyses. Y.M., O.R., A.T., and Y.S. wrote the manuscript with input from all the authors.",
year = "2023",
month = jun,
day = "8",
doi = "https://doi.org/10.1016/j.cell.2023.04.037",
language = "الإنجليزيّة",
volume = "186",
pages = "2610--2627.e18",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "12",
}