Disentangling cell-intrinsic and cell-extrinsic factors underlying evolution.

ABSTRACT: 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 misexpres

SUBMITTER: Starr AL 

PROVIDER: S-EPMC12366658 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature