PhD Scientific Days 2017

Oral Presentations: Neurosciences

Using an isogenic human induced pluripotent stem cell lines to study the role of disrupted in schizophrenia 1 gene in hippocampal neurogenesis

Előadó neve

Hathy, Edit

Előadó munkahelye

Molecular Psychiatry Research Group, National Brain Research Program (NAP), Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

+36/30-5367456

Előadó e-mail címe

hathyedit@gmail.com

Az előadás címe

Using an isogenic human induced pluripotent stem cell lines to study the role of disrupted in schizophrenia 1 gene in hippocampal neurogenesis

Szerző(k) neve és munkahelye

Edit Hathy1, Sára Kálmán2, László Homolya3, Ágota Apáti3, Zsófia Nemoda1, János Réthelyi1,4
1 Molecular Psychiatry Research Group, National Brain Research Program (NAP), Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
2 Department of Psychiatry, University of Szeged, Szeged, Hungary
3 Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary
4 Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary

Szekció

Oral Presentations: Neurosciences

Data of the presenter

Doctoral school: 4. Doctoral School of Mental Health Sciences
Program: 1. Psychiatry
Supervisor: János Réthelyi
E-mail: hathyedit@gmail.com

Text of the abstract

Disrupted in schizophrenia 1 (DISC1) gene has been extensively studied over the last decades after the description of a balanced translocation of t(1;11)(q42.1;q14.3) in a multigenerational Scottish family with several cases of psychosis and affective disorders. Molecular biological experiments have shown that DISC1 protein interacts with various cytoskeletal and centrosome proteins, affecting neuronal proliferation and migration, spine regulation and synapse maintenance.
Induced pluripotent stem cells (IPSCs) are a potentially novel source of cell-based models to investigate neuronal differentiation and molecular pathways in healthy and diseased conditions. Moreover using this model system the role of specific genes or pathways can be examined. In this study we use an isogenic IPSC line to study the role of DISC1 in a model of hippocampal dentate gyrus (GD) neurogenesis, given that faulty hippocampal neurogenesis has been implicated in several psychiatric disorders. IPSC line XCL1 was engineered using zinc finger nuclease technology to produce an isogenic DISC1 exon2 biallelic knockout cell line (XCL1 DISCI exon2 KO/KO). The isogenic IPSC pair was characterized in terms of pluripotency and spontaneous differentiation potential. Next, IPSC lines were differentiated into neuronal lineages using established protocols to generate hippocampal dentate gyrus granule cells. The GD protocol is based on dual SMAD inhibition, Wnt- and SHH inhibition, which results in forebrain specific Sox2 and Nestin positive neuronal progenitor cells (NPCs). This intermediate cell type can be further differentiated into PROX1 and MAP2 expressing mature neurons. NPCs and neurons were characterized using immunofluorescence staining and qPCR.
The generated neuronal progenitors and mature neurons are amenable for assays comparing the isogenic pairs by immunofluorescence microscopy, transcriptomics, calcium-imaging and real-time visualization of neurite outgrowth. These investigations may shed light on the role of DISC1 in hippocampal neurogenesis and the etiology of psychiatric disorders.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1189

Authors (legacy)

Edit Hathy1, Sára Kálmán2, László Homolya3, Ágota Apáti3, Zsófia Nemoda1, János Réthelyi1,4
1 Molecular Psychiatry Research Group, National Brain Research Program (NAP), Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
2 Department of Psychiatry, University of Szeged, Szeged, Hungary
3 Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary
4 Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary