Mapping transcription factor functions in astrocytes using in vivo gain-of-function Perturb-seq
Summary
An in vivo approach combining high-throughput screening with cell type-specific readouts could enable elucidation of genotype-phenotype relationships in complex tissues. We developed an in vivo gain-of-function Perturb-seq platform, termed iGOF-Perturb-seq, to build a functional atlas of ~1000 transcription factors (TFs) in astrocytes, a cell type essential to many brain functions. We then identified cofunctional modules, annotated uncharacterized TFs, and predicted disease-associated TF c
Content
# Mapping transcription factor functions in astrocytes using in vivo gain-of-function Perturb-seq
*Published: 2026 Apr 23*
An in vivo approach combining high-throughput screening with cell type-specific
readouts could enable elucidation of genotype-phenotype relationships in complex
tissues. We developed an in vivo gain-of-function Perturb-seq platform, termed
iGOF-Perturb-seq, to build a functional atlas of ~1000 transcription factors
(TFs) in astrocytes, a cell type essential to many brain functions. We then
identified cofunctional modules, annotated uncharacterized TFs, and predicted
disease-associated TF clusters. Furthermore, iGOF-Perturb-seq performed in a
mouse neuroinflammatory model identified Ferd3l as a therapeutic candidate, and
astrocyte-specific overexpression of Ferd3l alleviated Alzheimer's disease
symptoms in mice. This study provides resources for understanding gene
regulation and disease mechanisms in vivo and for identifying potential
therapeutic targets for different brain diseases.
DOI: 10.1126/science.adw2156