@article{944ac7fd26a146a6bad2b3e5f43b4ef0,
title = "A stem cell zoo uncovers intracellular scaling of developmental tempo across mammals",
abstract = "Differential speeds in biochemical reactions have been proposed to be responsible for the differences in developmental tempo between mice and humans. However, the underlying mechanism controlling the species-specific kinetics remains to be determined. Using in vitro differentiation of pluripotent stem cells, we recapitulated the segmentation clocks of diverse mammalian species varying in body weight and taxa: marmoset, rabbit, cattle, and rhinoceros. Together with mousee and human, the segmentation clock periods of the six species did not scale with the animal body weight, but with the embryogenesis length. The biochemical kinetics of the core clock gene HES7 displayed clear scaling with the species-specific segmentation clock period. However, the cellular metabolic rates did not show an evident correlation. Instead, genes involving biochemical reactions showed an expression pattern that scales with the segmentation clock period. Altogether, our stem cell zoo uncovered general scaling laws governing species-specific developmental tempo.",
keywords = "allochrony, developmental tempo, segmentation clock, stem cell zoo",
author = "Jorge L{\'a}zaro and Maria Costanzo and Marina Sanaki-Matsumiya and Charles Girardot and Masafumi Hayashi and Katsuhiko Hayashi and Sebastian Diecke and Hildebrandt, {Thomas B.} and Giovanna Lazzari and Jun Wu and Stoyan Petkov and R{\"u}diger Behr and Vikas Trivedi and Mitsuhiro Matsuda and Miki Ebisuya",
note = "Funding Information: This work was supported by EMBL ; the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation program (grant agreement no. 101002564 ) (to M.E.); Takeda Science Foundation (to M.E.); project PGC2018-097872-A-I00 (MCIU/AEI/FEDER, UE) funded by the Spanish Ministry of Science, Innovation and Universities (MCIU) and co-funded by the European Regional Development Fund (ERDF, EU) (to M.E.); PRESTO (grant number JP20332265 ) from Japan Science and Technology Agency (JST) (to M.M.); the Boehringer Ingelheim Fonds (BIF) PhD fellowship (to J.L.); the Japan Society for the Promotion of Science (JSPS) fellowship (to M.S.-M.); and the Deutsches Zentrum f{\"u}r Herz-Kreislauf-Forschung (grant number 81Z0300201 ) (to R.B.). M.E. is supported by the Alexander von Humboldt Foundation in the framework of the Alexander von Humboldt Professorship endowed by the Federal Ministry of Education and Research. J.W. is a New York Stem Cell Foundation–Robertson Investigator and Virginia Murchison Linthicum Scholar in Medical Research. Funding Information: The human, mouse, and rabbit PSC lines were provided by the RIKEN BRC through the National BioResource Project of the MEXT, Japan. Funding Information: This work was supported by EMBL; the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 101002564) (to M.E.); Takeda Science Foundation (to M.E.); project PGC2018-097872-A-I00 (MCIU/AEI/FEDER, UE) funded by the Spanish Ministry of Science, Innovation and Universities (MCIU) and co-funded by the European Regional Development Fund (ERDF, EU) (to M.E.); PRESTO (grant number JP20332265) from Japan Science and Technology Agency (JST) (to M.M.); the Boehringer Ingelheim Fonds (BIF) PhD fellowship (to J.L.); the Japan Society for the Promotion of Science (JSPS) fellowship (to M.S.-M.); and the Deutsches Zentrum f{\"u}r Herz-Kreislauf-Forschung (grant number 81Z0300201) (to R.B.). M.E. is supported by the Alexander von Humboldt Foundation in the framework of the Alexander von Humboldt Professorship endowed by the Federal Ministry of Education and Research. J.W. is a New York Stem Cell Foundation–Robertson Investigator and Virginia Murchison Linthicum Scholar in Medical Research. The human, mouse, and rabbit PSC lines were provided by the RIKEN BRC through the National BioResource Project of the MEXT, Japan. We are thankful for the members of the Ebisuya lab for advice and critical feedback during the whole duration of the project; for J{\'u}lia Charles Aymam{\'i} for designing the animal icons and stem cell zoo logo; for Guillermo Mart{\'i}nez Ara for helping perform imaging experiments and image analysis during the revision stage and for commenting on the manuscript; for Teresa Rayon for experimental advice and for commenting on the manuscript; for Jaroslaw Sochacki for advice on the culture of stem cells; for the BIF network for the feedback during the progress meetings; for the Flow Cytometry Unit of the Center for Genomic Regulation for consultation in data acquisition and analysis; for Jelle Scholtalbers from Genome Biology Computational Support for support with the EMBL Galaxy platform; for Fumio Nakaki for advice in RNA-seq data analysis; for Joaquina Delas Vives for experimental advice; for Gregor M{\"o}nke for implementing features into pyBOAT that facilitated the analysis of the data; for Susanne Holtze, Frank G{\"o}ritz, and Robert Hermes from the Leibniz Institute for Zoo and Wildlife Research for participating in the rhinoceros semen and oocyte collections necessary to produce the rhinoceros ESC line; for Michal Zaluski and his staff for their support during the rhinoceros oocyte collection at the Silesian Zoological Garden in Chorzow; for Miriam Wiesner and her staff for their participation during the rhinoceros semen collection at the Salzburg Zoo; for Cesare Galli and Silvia Colleoni for their input during the in vitro production of the rhinoceros embryos; for Juan Carlos Izpisua Belmonte for facilitating the obtention of cattle ESCs; for Shinya Yamanaka and CiRA for facilitating the obtention of the human iPSCs; for Arata Honda for depositing the rabbit ESC in the RIKEN BRC; and for Milena Marinkovic, Carina Vibe, Marc Duque Ram{\'i}rez, and James Briscoe for their comments on the manuscript. M.M. and M.E. conceived the project. J.L. performed most of the experiments and analyzed the data. M.M. provided advice and performed experiments with human and mouse PSCs. M.C. and M.S.-M. optimized cattle cell culture and performed experiments with cattle ESCs. C.G. performed gene expression analyses from the raw bulk RNA-seq data and assembled the multi-species gene ortholog table. M.H. and K.H. provided a table of orthologous genes between humans, mice, and rhinoceros. S.D. T.B.H. and G.L. provided the rhinoceros ESCs and advice to culture them. J.W. provided the cattle ESCs and advice to culture them. S.P. and R.B. provided the marmoset iPSCs and advice to culture them. J.L. and M.E. wrote the manuscript with feedback from all authors. M.E. M.M. and V.T. supervised the project. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = jul,
day = "6",
doi = "10.1016/j.stem.2023.05.014",
language = "English (US)",
volume = "30",
pages = "938--949.e7",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "7",
}