Authors
VÁŇOVÁ, Tereza; Jiří SEDMÍK; Jan RAŠKA; Kateřina AMRUZ ČERNÁ; Petr TAUŠ; Veronika POSPÍŠILOVÁ; Markéta NEZVEDOVÁ; Veronika FEDOROVÁ; Soňa KADÁKOVÁ; Hana KLÍMOVÁ; Michaela CAPANDOVÁ; Petra ORVISKÁ; Petr FOJTÍK; Simona BÁRTOVÁ; Karla PLEVOVÁ; Zdeněk SPÁČIL; Hana HŘÍBKOVÁ and Dáša BOHAČIAKOVÁ
Edition
CELL REPORTS, UNITED STATES, CELL PRESS, 2023, 2211-1247
Links
CZ.02.1.01/0.0/0.0/16_013/0001761, interní kód Repo. EF15_003/0000469, research and development project. EF16_013/0001761, research and development project. EF17_043/0009632, research and development project. EF19_073/0016943, research and development project. GA20-15728S, research and development project. GA21-21510S, research and development project. LX22NPO5107, research and development project. MUNI/A/1301/2022, interní kód Repo. MUNI/G/1131/2017, interní kód Repo. MUNI/IGA/1273/2021, interní kód Repo. MUNI/R/1321/2021, interní kód Repo. MUNI/R/1697/2020, interní kód Repo. NU20-08-00314, research and development project. NU21-08-00373, research and development project. NU22J-08-00075, research and development project. NU22-04-00366, research and development project. NV19-08-00472, research and development project. 101087124, interní kód Repo. 8F20009, research and development project. 857560, interní kód Repo. RECETOX RI, large research infrastructures. Czech-BioImaging II, large research infrastructures. NCMG II, large research infrastructures.
In the original language
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.