Pluto Bioinformatics

GSE146672: Single cell RNA sequencing of P7 cortex from Top1 knockout mice

Bulk RNA sequencing

Topoisomerase 1 (TOP1) relieves torsional stress in DNA during transcription and facilitates the expression of long (>100 kb) genes, many of which are important for neuronal functions. To evaluate how loss of Top1 affected neurons in vivo, we conditionally deleted (cKO) Top1 in postmitotic excitatory neurons in the mouse cerebral cortex and hippocampus. We found that Top1 cKO neurons developed properly but then showed biased transcriptional downregulation of long genes, signs of DNA damage, neuroinflammation, increased poly(ADP-ribose) polymerase-1 (PARP1) activity, single-cell somatic mutations, and ultimately degenerated. We used single-cell RNA-seq to verify cell-type decreases in long-gene expression as well as investigate how TOP1 loss may lead to premature neuronal death. SOURCE: Jesse Niehaus (kylius0@email.unc.edu) - Zylka Lab University of North Carolina at Chapel Hill