Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00078436" target="_blank" >RIV/00159816:_____/23:00078436 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/23:00132029 RIV/65269705:_____/23:00078436

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S2211124723013220?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2211124723013220?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.celrep.2023.113310" target="_blank" >10.1016/j.celrep.2023.113310</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development

Popis výsledku v původním jazyce

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&apos;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 demon-strated 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 uncover-ing that neurons in AD-COs likely differentiate prematurely.

Název v anglickém jazyce

Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development

Popis výsledku anglicky

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&apos;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 demon-strated 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 uncover-ing that neurons in AD-COs likely differentiate prematurely.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cell Reports

ISSN

2211-1247

e-ISSN

2211-1247

Svazek periodika

42

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

27

Strana od-do

113310

Kód UT WoS článku

001096821600001

EID výsledku v databázi Scopus

2-s2.0-85174468116