Astrocytic-supplied cholesterol drives synaptic gene expression programs in developing neurons and downstream astrocytic transcriptional programs.

ABSTRACT: Astrocytes participate in neuronal synaptic programs that are enriched for genetic associations in schizophrenia and autism spectrum disorders (ASD). To better understand how these co-regulated cellular programs are induced during early neuronal development, we studied astrocytes and iPSC-derived neurons in co-cultures and mono-cultures at 16 time points spanning 0.5 hours to 8 days. We found that upregulation in astrocytes of genes involved in cholesterol biosynthesis preceded the activation of synaptic gene programs in neurons and upregulation of the astrocytic Nrxn1. Neuronal knockdown of key cholesterol receptors led to downregulation of neuronal synaptic genes and induced a robust transcriptional response in the astrocytes, including further upregulation of Nrxn1. This s

SUBMITTER: Vartiainen E 

PROVIDER: S-EPMC11838310 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature