A stem cell zoo uncovers intracellular scaling of developmental tempo across mammals

干细胞动物园揭示哺乳动物发育节奏的细胞内缩放

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作者:Jorge Lázaro, Maria Costanzo, Marina Sanaki-Matsumiya, Charles Girardot, Masafumi Hayashi, Katsuhiko Hayashi, Sebastian Diecke, Thomas B Hildebrandt, Giovanna Lazzari, Jun Wu, Stoyan Petkov, Rüdiger Behr, Vikas Trivedi, Mitsuhiro Matsuda, Miki Ebisuya

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 mouse 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.

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