論文 - 詳細
| RRC ID | 88310 |
|---|---|
| 著者 | Krontira AC, Cruceanu C, Dony L, Kyrousi C, Link MH, Rek N, Pöhlchen D, Raimundo C, Penner-Goeke S, Schowe A, Czamara D, Lahti-Pulkkinen M, Sammallahti S, Wolford E, Heinonen K, Roeh S, Sportelli V, Wölfel B, Ködel M, Sauer S, Rex-Haffner M, Räikkönen K, Labeur M, Cappello S, Binder EB. |
| タイトル | Human cortical neurogenesis is altered via glucocorticoid-mediated regulation of ZBTB16 expression. |
| ジャーナル | Neuron |
| Abstract |
Glucocorticoids are important for proper organ maturation, and their levels are tightly regulated during development. Here, we use human cerebral organoids and mice to study the cell-type-specific effects of glucocorticoids on neurogenesis. We show that glucocorticoids increase a specific type of basal progenitors (co-expressing PAX6 and EOMES) that has been shown to contribute to cortical expansion in gyrified species. This effect is mediated via the transcription factor ZBTB16 and leads to increased production of neurons. A phenome-wide Mendelian randomization analysis of an enhancer variant that moderates glucocorticoid-induced ZBTB16 levels reveals causal relationships with higher educational attainment and altered brain structure. The relationship with postnatal cognition is also supported by data from a prospective pregnancy cohort study. This work provides a cellular and molecular pathway for the effects of glucocorticoids on human neurogenesis that relates to lasting postnatal phenotypes. |
| 巻・号 | 112(9) |
| ページ | 1426-1443.e11 |
| 公開日 | 2024-5-1 |
| DOI | 10.1016/j.neuron.2024.02.005 |
| PII | S0896-6273(24)00089-8 |
| PMID | 38442714 |
| MeSH | Animals Cerebral Cortex* / cytology Cerebral Cortex* / drug effects Cerebral Cortex* / metabolism Female Gene Expression Regulation, Developmental / drug effects Glucocorticoids* / pharmacology Humans Male Mice Neural Stem Cells / drug effects Neural Stem Cells / metabolism Neurogenesis* / drug effects Neurogenesis* / physiology Neurons / drug effects Neurons / metabolism Organoids / drug effects Organoids / metabolism Pregnancy Promyelocytic Leukemia Zinc Finger Protein* / metabolism |
| リソース情報 | |
| ヒト・動物細胞 | 409B2(HPS0076) |