A developmental program that regulates mammalian organ size offsets evolutionary distance Institutional Repository Document uri icon


  • AbstractPigs 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

altmetric score

  • 8.184

author list (cited authors)

  • Shimamura, Y., Tanaka, J., Kakiuchi, M., Sarmah, H., Miura, A., Hwang, Y., ... Mori, M.

citation count

  • 0

complete list of authors

  • Shimamura, Yuko||Tanaka, Junichi||Kakiuchi, Miwako||Sarmah, Hemanta||Miura, Akihiro||Hwang, Youngmin||Sawada, Anri||Ninish, Zurab||Yamada, Kazuhiko||Cai, James J||Mori, Munemasa

Book Title

  • bioRxiv

publication date

  • October 2022