|
| Status |
Public on Sep 15, 2021 |
| Title |
Fetal Growth Restriction Impairs Hippocampal Neurogenesis and Cognition via Tet1 in Offspring |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Fetal growth restriction (FGR) increases the risk for impaired cognitive function later in life. However, the precise mechanisms remain elusive. Using dexamethasone-induced FGR and protein restriction-influenced FGR mouse models, we observed learning and memory deficits in adult FGR offspring. FGR induces decreased hippocampal neurogenesis from the early postnatal period to adulthood by reducing the proliferation of neural stem cells (NSCs). We further found a persistent decrease of Tet1 expression in hippocampal NSCs of FGR mice. Mechanistically, Tet1 downregulation results in hypermethylation of the Dll3 and Notch1 promoters and inhibition of Notch signaling, leading to reduced NSC proliferation. Overexpression of Tet1 activates Notch signaling, offsets the decline in neurogenesis, and enhances learning and memory abilities in FGR offspring. Our data indicate that a long-term decrease in Tet1/Notch signaling in hippocampal NSCs contributes to impaired neurogenesis following FGR and could serve as potential targets for the intervention of FGR-related cognitive disorders.
|
| |
|
| Overall design |
The hippocampi were obtained from NS and IUGR male C57BL/6J mice at postnatal day 3 and week 8.
|
| |
|
| Contributor(s) |
Chen W, Shen S, Jiang C, Kang J |
| Citation(s) |
34731622 |
| Submission date |
Jan 16, 2020 |
| Last update date |
Nov 12, 2021 |
| Contact name |
Shijun Shen |
| E-mail(s) |
xiaoshen19930901@163.com
|
| Phone |
+86-21-13795384821
|
| Organization name |
Tongji University
|
| Department |
Bioninformatics
|
| Lab |
Jiang Lab
|
| Street address |
1239 Siping Road, Shanghai, P.R. China
|
| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200092 |
| Country |
China |
| |
|
| Platforms (1) |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA601762 |
| SRA |
SRP242297 |
Less...
More...