Transcriptomics

Dataset Information

0

Human iPSC 4R tauopathy model uncovers modifiers of tau propagation [scRNA-seq]


ABSTRACT: Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to lack of appropriate human models. Here, we engineered new human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer’s Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE255904 | GEO | 2024/04/08

REPOSITORIES: GEO

Dataset's files

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

Similar Datasets

2024-04-08 | GSE255902 | GEO
2022-04-26 | GSE201084 | GEO
2019-06-23 | GSE118473 | GEO
2021-03-24 | GSE169478 | GEO
2021-12-02 | E-MTAB-10985 | biostudies-arrayexpress
| PRJNA1076934 | ENA
2020-10-27 | GSE160151 | GEO
| PRJNA1076936 | ENA
2023-12-08 | GSE242693 | GEO
2023-12-08 | GSE242180 | GEO