Reference - Detail
| RRC ID | 85777 |
|---|---|
| Author | Dony L, Krontira AC, Kaspar L, Ahmad R, Demirel IS, Grochowicz M, Schäfer T, Begum F, Sportelli V, Raimundo C, Koedel M, Labeur M, Cappello S, Theis FJ, Cruceanu C, Binder EB. |
| Title | Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids. |
| Journal | Sci Adv |
| Abstract |
Disruptions in the tightly regulated process of human brain development have been linked to increased risk for brain and mental illnesses. While the genetic contribution to these diseases is well established, important environmental factors have been less studied at molecular and cellular levels. Here, we used single-cell and cell type-specific techniques to investigate the effect of glucocorticoid (GC) exposure, a mediator of antenatal environmental risk, on gene regulation and lineage specification in unguided human neural organoids. We characterized the transcriptional response to chronic GC exposure during neural differentiation and studied the underlying gene regulatory networks by integrating single-cell transcriptomics with chromatin accessibility data. We found lasting cell type-specific changes that included autism risk genes and several transcription factors associated with neurodevelopment. Chronic GC exposure influenced lineage specification primarily by priming the inhibitory neuron lineage through transcription factors like PBX3. We provide evidence for convergence of genetic and environmental risk factors through a common mechanism of altering lineage specification. |
| Volume | 11(7) |
| Pages | eadn8631 |
| Published | 2025-2-14 |
| DOI | 10.1126/sciadv.adn8631 |
| PMID | 39951527 |
| PMC | PMC11827642 |
| MeSH | Cell Differentiation / drug effects Cell Lineage / drug effects Gene Regulatory Networks / drug effects Glucocorticoids* / pharmacology Humans Neurogenesis* / drug effects Neurogenesis* / genetics Neurons* / cytology Neurons* / drug effects Neurons* / metabolism Organoids* / cytology Organoids* / drug effects Organoids* / metabolism Single-Cell Analysis Transcription Factors / metabolism |
| IF | 13.117 |
| Resource | |
| Human and Animal Cells | 409B2(HPS0076) |