mouse TF perturbation in mouse brain (PRJCA028495)
Transcription factors (TFs) are pivotal regulators of gene programs, orchestrating a myriad of cellular processes and states. To attain a holistic comprehension of TFs and the gene programs they govern, we have generated a barcoded library encompassing all the longest annotated mouse TF splice isoforms (~1100). This library has been utilized to construct a comprehensive TF Atlas, delineating the expression profiles of mouse brain astrocytes with each TF overexpressed at a single-cell resolution. We have correlated the pathway changes induced by the perturbation of each TF with data from human common brain diseases (AD, PD, HD, MS, ALS and FTLD), aging, and glioma, discovering that indeed many TF perturbations elicit pathway changes akin to those observed in neurodegenerative diseases. These findings have been corroborated through both in vivo and in vitro experiments. Such insights have significantly advanced our understanding of the roles played by distinct TFs within glial cells in the brain.