PhD Scientific Days 2025

Poster Session II. - B: Molecular Medicine

Development of a cerebellar organoid platform for investigating ataxia related molecular pathomechanisms

Előadó neve

Sándor Alexandra

Neptun code

FPA9ED

Előadó munkahelye

HUN-REN TTK

Előadó telefonszáma

+36303069298

Előadó e-mail címe

sandor.alexandra@phd.semmelweis.hu

Az előadás címe

Development of a cerebellar organoid platform for investigating ataxia related molecular pathomechanisms

Szerző(k) neve és munkahelye

Alexandra Sándor¹, Kornélia Szebényi¹

1: HUN-REN TTK

Bemutatás módja

Poszter

Szekció

Poster Session II. - B: Molecular Medicine

Language of the presentation

Hungarian

Preferred session

Molecular Medicine

Összefoglaló szövege

Spinocerebellar ataxias (SCA) represent a diverse range of neurological disorders, mainly
characterised by the slow degeneration of the cerebellum resulting in loss of motor co-ordination.
Given the distinct development, cell composition and size of the human cerebellum compared to
mice, human model systems are essential for studying neurodegenerative changes underlying
SCAs. Human induced pluripotent stem cell (hiPSC)-derived cerebellar organoid systems contain
the disease relevant cell types in a tissue-like organization and therefore can provide a relevant
model for investigating the molecular mechanisms of ataxias affecting the human cerebellum.
We have developed a protocol for the generation of a hiPSC-derived organoid model of the
cerebellum. The cell types found in the organoids on days 35, 50, 75 and 120 of the differentiation
were characterized by immunocytochemical methods, using markers specific to the developmental
stages of the cerebellum. We showed that Kirrel2-positive Purkinje progenitors appear on day 35,
from which Calbindin-positive Purkinje neurons develop by day 50. At this point astroglial cells
are also present in the cerebellar organoids. In order to prove that the model is also suitable for
detecting pathological changes, we treated the organoids with IL-1β, capable of inducing ataxia in
mice. IL-1β treatment evoked ER stress and increased the expression level of the ubiquitin-binding
protein P62.
In summary, we have created an organoid model of the human cerebellum, which is suitable for
examining cell-specific pathological changes and can serve as a platform for the development of
therapies targeting them.
Acknowledgement: We are greatful to Katalin Monostory and Ágota Apáti for providing laboratory spaces
and access to essential equipment. Project no. 2023-2.1.2-KDP-2023-00016 has been implemented with the
support provided by the Ministry of Culture and Innovation of Hungary from the National Research,
Development and Innovation Fund, financed under the KDP-2023 funding scheme.

University

Semmelweis University

Supervisor

Kornélia Szebényi

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8018

Start

18:12

End

18:18