PhD Scientific Days 2022

Mental Health Sciences III.

Induced pluripotent stem cell based in vitro disease modelling of schizophrenia: potential pathogenic role of a ZMYND11 de novo mutation

Előadó neve

Dr. Csongor, Tordai

Előadó munkahelye

Semmelweis University Psychiatry and Psychotherapy Clinic

Előadó telefonszáma

+36704906705

Előadó e-mail címe

tordaicsonge@gmail.com

Az előadás címe

Induced pluripotent stem cell based in vitro disease modelling of schizophrenia: potential pathogenic role of a ZMYND11 de novo mutation

Szerző(k) neve és munkahelye

Csongor Tordai1,2, Katalin Vincze1,2, Hathy Edit1, Póti Ádám2, Szűts Dávid2 , Ágota Apáti2, János Réthelyi1
1. Molecular Psychiatry Research Group, Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary
2. Molecular Cell Biology Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Mental Health Sciences III.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Our research group models neurodevelopmental psychiatric disorders in vitro using induced pluripotent stem cells. Earlier we reprogrammed somatic cells into pluripotent stem cells from a schizophrenia patient, carrying a functionally relevant de novo mutation in the ZMYND11 gene. Then we differentiated these stem cells into hippocampal neurons in vitro. To our current understanding, the hippocampus may play a pathogenic role in schizophrenia via dysregulation of glutamate neurotransmission. [1]

Aims: By genetic and functional analysis of these neurons carrying the genetic material of the schizophrenic patient, we aim to discover cellular processes relevant to disease pathogenesis; with a focus on glutamatergic neurotransmission.

Methods: With the help of CRISPR technology we created an isogenic control cell line by correcting the original mutation in the ZMYND11 gene. We used RNA sequencing to analyse the expression profiles of the in vitro differentiated hippocampal neurons. We used calcium imaging to quantify the cells’ reaction to glutamate stimulation.

Results: Surprisingly, genes responsible for glutamatergic neurotransmission, and genes that are associated with neuronal function were overexpressed in the mutant cell line compared to the control. On the contrary, ZMYND11 mutant cells showed decreased reaction to glutamate stimulation during calcium imaging experiments.

Conclusions: Our results showed the anticipated dysregulation of the glutamatergic neurotransmission in these in vitro differentiated hippocampal neurons originating from a schizophrenic patient. Based on our data, ZMYND11, a transcriptional modulator, may indeed be involved in the pathogenesis in this particular case of schizophrenia.

Funding: NAP 2017-1.2.1-NKP-2017-00002 grant, TKP2021-EGA-25, SE 250+ PhD grant

References:
[1] Lieberman, J.A., Girgis, R.R., Brucato, G. et al. Hippocampal dysfunction in the pathophysiology of schizophrenia: a selective review and hypothesis for early detection and intervention. Mol Psychiatry 23, 1764–1772 (2018). https://doi.org/10.1038/mp.2017.249

University and Doctoral School

Semmelweis University, Doctoral School of Mental Health Sciences

Supervisor

Dr. Ágota Apáti, Dr. János Réthelyi

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6015

Start

16:00

End

16:15

Authors (legacy)

Csongor Tordai1,2, Katalin Vincze1,2, Hathy Edit1, Póti Ádám2, Szűts Dávid2 , Ágota Apáti2, János Réthelyi1
1. Molecular Psychiatry Research Group, Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary
2. Molecular Cell Biology Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary