Transcriptomics

Dataset Information

0

Transcriptional Regulation by PHGDH Modulates Pathological Progression in a Human Brain Organoid Model of Late-Onset Alzheimer’s Disease


ABSTRACT: Phosphoglycerate Dehydrogenase (PHGDH), prominently expressed in brain astrocytes, exhibits heightened levels in the early stages of late-onset Alzheimer’s Disease (LOAD). We demonstrate that alterations in PHGDH expression within astrocytes in a human brain organoid model of LOAD induce pathological changes, independent of PHGDH’s canonical enzymatic role. Remarkably, PHGDH functions as a transcriptional regulator by binding to chromatin, as evidenced by ChIP-seq, snRNA-seq, knockdown, and mutation experiments. Our analysis identifies IKKa and HMGB1, regulators of NFκB and autophagy, as pivotal transcriptional targets of PHGDH. Dual knockdown of IKKa and HMGB1 in astrocytes effectively mitigates PHGDH-induced LOAD pathological changes in brain organoids, reducing Aβ aggregates, cell death, and NFκB activation while enhancing synaptic puncta and autophagy. These findings unveil a novel pathological pathway in LOAD, elucidating PHGDH’s role as a transcriptional regulator in disease progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE261164 | GEO | 2025/07/02

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2008-06-17 | E-GEOD-8555 | biostudies-arrayexpress
2007-07-25 | GSE8555 | GEO
2023-05-10 | PXD035586 | Pride
2022-03-30 | GSE198380 | GEO
2023-07-10 | GSE236429 | GEO
2021-07-29 | GSE180640 | GEO
2024-01-27 | GSE236357 | GEO
2023-06-13 | GSE224784 | GEO
2022-10-06 | PXD036321 | Pride
2021-11-01 | GSE179912 | GEO