2025-05-30 東京科学大学
<関連情報>
- https://www.isct.ac.jp/ja/news/nk4sxe0l05er
- https://www.isct.ac.jp/plugins/cms/component_download_file.php?type=2&pageId=&contentsId=1&contentsDataId=1366&prevId=&key=4b5ad3471ec07fe6eb0e6cc5757119c4.pdf
- https://www.cell.com/cell-genomics/fulltext/S2666-979X(25)00147-8
進化を支える細胞内因子と細胞外因子の分離 Disentangling cell-intrinsic and cell-extrinsic factors underlying evolution
Alexander L. Starr ∙ Toshiya Nishimura ∙ Kyomi J. Igarashi ∙ Chihiro Funamoto ∙ Hiromitsu Nakauchi ∙ Hunter B. Fraser
Cell Genomics Published:May 29, 2025
DOI:https://doi.org/10.1016/j.xgen.2025.100891
Highlights
- Cellular function is shaped by factors both intrinsic and extrinsic to every cell
- We invent a framework to decompose trait divergence into intrinsic/extrinsic components
- Rat-mouse chimeras show that most gene expression divergence is cell intrinsic
- Misexpression of imprinted genes suggests intrinsic/extrinsic incompatibilities
Summary
A long-standing question in biology is the extent to which cells function autonomously as opposed to requiring interactions with other cells or environmental factors. Here, we develop a framework to use interspecies chimeras to precisely decompose evolutionary divergence in any cellular trait into cell-intrinsic and cell-extrinsic components. Applying this framework to thousands of gene expression levels in reciprocal rat-mouse chimeras, we found that most divergence is cell intrinsic, though extrinsic factors also play an integral role. For example, cell-extrinsic regulation of a transcription factor can propagate to its target genes, leading to cell-type-specific extrinsic regulation of both their mRNA and their protein levels. We also show that imprinted genes are dramatically misexpressed in chimeras, suggesting a mismatch between rapidly evolving intrinsic and extrinsic imprinting mechanisms. Overall, our conceptual framework opens up new avenues to investigate the mechanistic basis of the evolution, development, and regulation of myriad cellular traits in any multicellular organism.
