| Experiment Id | GSE146672 | Name | Single cell RNA sequencing of P7 cortex from Top1 knockout mice |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2022-09-23 |
| description | 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. Topoisomerase I(Top1) f/f mice were crossed with Top1 f/+; NEX-cre mice to generate Top1 f/f; NEX-cre animals where Top1 is conditionally knocked out of cortical and hippocampal excitatory neurons. Cortical tissue was dissociated into single-cell suspensions from Top1 f/f;NEX-cre mice (n=2) and littermate controls (NEX-cre negative; n=2) at postnatal day 7. Single-cell transcriptomes were generated using the microfluidic approach known as Dropseq. |
