RT Journal Article
SR Electronic
T1 A developmental program that regulates mammalian organ size offsets evolutionary distance
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.10.19.512107
DO 10.1101/2022.10.19.512107
A1 Yuko Shimamura
A1 Junichi Tanaka
A1 Miwako Kakiuchi
A1 Hemanta Sarmah
A1 Akihiro Miura
A1 Youngmin Hwang
A1 Anri Sawada
A1 Zurab Ninish
A1 Kazuhiko Yamada
A1 James J. Cai
A1 Munemasa Mori
YR 2022
UL http://biorxiv.org/content/early/2022/10/21/2022.10.19.512107.abstract
AB 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 Summary A cross-species developmental molecular atlas identified the indicator of lung and animal size beyond evolutionCompeting Interest StatementThe authors have declared no competing interest.