A developmental program that regulates mammalian organ size offsets evolutionary distance

Shimamura, Y.; Tanaka, J.; Kakiuchi, M.; Sarmah, H.; Miura, A.; Hwang, Y.; Sawada, A.; Ninish, Z.; Yamada, K.; Cai, J. J.; Mori, M.

doi:10.1101/2022.10.19.512107

bioRxiv · 10.1101/2022.10.19.512107

A developmental program that regulates mammalian organ size offsets evolutionary distance

Shimamura, Y.·Tanaka, J.·Kakiuchi, M.·Sarmah, H.·Miura, A.·Hwang, Y.·Sawada, A.·Ninish, Z.·Yamada, K.·Cai, J. J.·Mori, M.

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Abstract

Pigs are evolutionarily more distant from humans than mice, but their physiological organs are closest to humans. The molecular program leading to a more than 1,000-fold increase in organ size in pigs and humans over that of mice across evolution has not been elucidated. We generated large-scale transcriptional landscapes throughout swine lung development. Our cross-species single-cell molecular atlas let us discover swine progenitor identities, stage-specific markers, and a core organ-size regulation program (COSRP), well-conserved in swine and humans but less so in mice. Across eight mammalian species, human COSRP promoters showed higher homologies to evolutionary-distant large animals, including pigs, than evolutionary-close small animals. Our study provides a molecular foundation during swine lung development that unveils animal size regulation conserved in the COSRP promoter, independent of genome-wide evolution. COSRP is a critical paradigm for studying thousands-fold changes in biological sizes in evolution, development, cancer, zoology, respirology, organoids, and biotechnology, particularly human-compatible organ generation. One Sentence SummaryA cross-species developmental molecular atlas identified the indicator of lung and animal size beyond evolution

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Shimamura, Y., Tanaka, J., Kakiuchi, M., Sarmah, H., Miura, A., Hwang, Y., Sawada, A., Ninish, Z., Yamada, K., Cai, J. J., Mori, M.. 2022-10-21. A developmental program that regulates mammalian organ size offsets evolutionary distance. https://doi.org/10.1101/2022.10.19.512107

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