Gonadal sex reversal at single-cell resolution in Znrf3-deficient mice.

ABSTRACT: The role of anti-WNT ZNRF3 is central to determining gonadal fate: XY mice lacking functional ZNRF3 exhibit a highly variable gonadal sex reversal phenotype in the fetal period, characterised by appearance of ovarian tissue. To investigate this sex reversal further, we used single-cell RNA-seq to examine the transcriptomes of XY Znrf3-deficient gonads during the mouse sex-determining period. Analyses of cell trajectories in mutant gonads reveal the failure of pre-supporting cells to commit to the Sertoli cell fate, XY granulosa cell development, unstable commitment in those cells that reach the Sertoli path and enhanced contribution to a supporting-like cell fate. By developing a machine learning-based score for transcriptomic similarity to Sertoli and granulosa, we show pervasive disrupti

SUBMITTER: Kay RGG 

PROVIDER: S-EPMC11658683 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature