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@article{1826918,
author = {Ibrahim, Akkouh and Hříbková, Hana and Grabiec, Marta and Budinská, Eva and Szabo, Attila and Kašpárek, Tomáš and Ole, Andreassen A. and Sun, YuhandMan and Djurovic, Srdjan},
article_location = {Oxford},
article_number = {1},
doi = {http://dx.doi.org/10.1093/schbul/sbab092},
keywords = {hiPSC; astrocyte diversity; transcription; glutamate; d-serine},
language = {eng},
issn = {0586-7614},
journal = {SCHIZOPHRENIA BULLETIN},
title = {Derivation and Molecular Characterization of a Morphological Subpopulation of Human iPSC Astrocytes Reveal a Potential Role in Schizophrenia and Clozapine Response},
url = {https://academic.oup.com/schizophreniabulletin/article/48/1/190/6343183},
volume = {48},
year = {2022}
}
TY - JOUR
ID - 1826918
AU - Ibrahim, Akkouh - Hříbková, Hana - Grabiec, Marta - Budinská, Eva - Szabo, Attila - Kašpárek, Tomáš - Ole, Andreassen A. - Sun, Yuh-Man - Djurovic, Srdjan
PY - 2022
TI - Derivation and Molecular Characterization of a Morphological Subpopulation of Human iPSC Astrocytes Reveal a Potential Role in Schizophrenia and Clozapine Response
JF - SCHIZOPHRENIA BULLETIN
VL - 48
IS - 1
SP - 190-198
EP - 190-198
PB - Oxford University Press
SN - 05867614
KW - hiPSC
KW - astrocyte diversity
KW - transcription
KW - glutamate
KW - d-serine
UR - https://academic.oup.com/schizophreniabulletin/article/48/1/190/6343183
N2 - Astrocytes are the most abundant cell type in the human brain and are important regulators of several critical cellular functions, including synaptic transmission. Although astrocytes are known to play a central role in the etiology and pathophysiology of schizophrenia, little is known about their potential involvement in clinical response to the antipsychotic clozapine. Moreover, astrocytes display a remarkable degree of morphological diversity, but the potential contribution of astrocytic subtypes to disease biology and drug response has received little attention. Here, we used state-of-the-art human induced pluripotent stem cell (hiPSC) technology to derive a morphological subtype of astrocytes from healthy individuals and individuals with schizophrenia, including responders and nonresponders to clozapine. Using functional assays and transcriptional profiling, we identified a distinct gene expression signature highly specific to schizophrenia as shown by disease association analysis of more than 10 000 diseases. We further found reduced levels of both glutamate and the NMDA receptor coagonist D-serine in subtype astrocytes derived from schizophrenia patients, and that exposure to clozapine only rescued this deficiency in cells from clozapine responders, providing further evidence that D-serine in particular, and NMDA receptor-mediated glutamatergic neurotransmission in general, could play an important role in disease pathophysiology and clozapine action. Our study represents a first attempt to explore the potential contribution of astrocyte diversity to schizophrenia pathophysiology using a human cellular model. Our findings suggest that specialized subtypes of astrocytes could be important modulators of disease pathophysiology and clinical drug response, and warrant further investigations.
ER -
IBRAHIM, Akkouh, Hana HŘÍBKOVÁ, Marta GRABIEC, Eva BUDINSKÁ, Attila SZABO, Tomáš KAŠPÁREK, Andreassen A. OLE, Yuh-Man SUN and Srdjan DJUROVIC. Derivation and Molecular Characterization of a Morphological Subpopulation of Human iPSC Astrocytes Reveal a Potential Role in Schizophrenia and Clozapine Response. \textit{SCHIZOPHRENIA BULLETIN}. Oxford: Oxford University Press, 2022, vol.~48, No~1, p.~190-198. ISSN~0586-7614. Available from: https://dx.doi.org/10.1093/schbul/sbab092.
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