Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
37864790
DOI
10.1016/j.celrep.2023.113310
PII: S2211-1247(23)01322-0
Knihovny.cz E-zdroje
- Klíčová slova
- Alzheimer’s disease, CP: Developmental biology, CP: Neuroscience, cerebral organoids, development, induced pluripotent stem cells, single-cell mRNA sequencing,
- MeSH
- Alzheimerova nemoc * genetika patologie MeSH
- indukované pluripotentní kmenové buňky patologie MeSH
- lidé MeSH
- mutace genetika MeSH
- neurony MeSH
- organoidy patologie MeSH
- presenilin-1 * genetika MeSH
- presenilin-2 * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- presenilin-1 * MeSH
- presenilin-2 * MeSH
- PSEN1 protein, human MeSH Prohlížeč
- PSEN2 protein, human MeSH Prohlížeč
During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study human neural development and disease. Especially in the field of Alzheimer's disease (AD), remarkable effort has been put into investigating molecular mechanisms behind this disease. Then, with the advent of 3D neuronal cultures and cerebral organoids (COs), several studies have demonstrated that this model can adequately mimic familial and sporadic AD. Therefore, we created an AD-CO model using iPSCs derived from patients with familial AD forms and explored early events and the progression of AD pathogenesis. Our study demonstrated that COs derived from three AD-iPSC lines with PSEN1(A246E) or PSEN2(N141I) mutations developed the AD-specific markers in vitro, yet they also uncover tissue patterning defects and altered development. These findings are complemented by single-cell sequencing data confirming this observation and uncovering that neurons in AD-COs likely differentiate prematurely.
Central European Institute of Technology Masaryk University 62500 Brno Czech Republic
RECETOX Faculty of Science Masaryk University 62500 Brno Czech Republic
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