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Derived Primate-Specific Astroglia Reveal Brain Disorder Traits

29 Pages Posted: 13 Jan 2020 Sneak Peek Status: Under Review

See all articles by Yuh-Man Sun

Yuh-Man Sun

Masaryk University - Department of Biology

Hana Hribkova

Masaryk University - Department of Biology

Ibrahim Akkouh

University of Oslo - NORMENT

Marta Grabiec

Masaryk University - Department of Biology

Eva Budinska

Masaryk University - Bioinformatics in Translational Research

Attila Szabo

University of Oslo - NORMENT

Tomas Kasparek

University Hospital Brno

Srdjan Djurovic

University of Oslo - Department of Medical Genetics

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Abstract

The biological functions of primate-specific astroglia, interlaminar astrocytes (IAs), remain enigmatic due to the lack of access to experimental materials, especially in humans. Here, we develop a protocol for the derivation of IAs from healthy normal and schizophrenia patient (SCZ)-specific human pluripotent stem cells. We find that IAs possess a functional profile which is distinct from that of protoplasmic astrocytes, particularly in synapse-associated functions such as neuroactive ligand-receptor interactions, calcium signaling, and long-term potentiation. These synaptic functions are further corroborated by our findings that IAs respond to glutamate, which mediates Ca2+ signaling and in turn leads to the release of gliotransmitters to interact with neurons and astrocytes. We further show that SCZ IAs shift their functional characteristic from synaptic signaling to Matrix-associated functions, with a notable impairment in the levels of gliotransmitters. We anticipate that these findings will prompt more penetrating investigations into the role of IAs in glia biology and brain disorders.

Keywords: primate-specific astroglia, interlaminar astrocytes, transcriptome profiling, gliotransmitters, human pluripotent stem cells, cneuron-astrocyte interaction, schizophrenia

Suggested Citation

Sun, Yuh-Man and Hribkova, Hana and Akkouh, Ibrahim and Grabiec, Marta and Budinska, Eva and Szabo, Attila and Kasparek, Tomas and Djurovic, Srdjan, Derived Primate-Specific Astroglia Reveal Brain Disorder Traits. CELL-STEM-CELL-D-19-00891. Available at SSRN: https://ssrn.com/abstract=3517534 or http://dx.doi.org/10.2139/ssrn.3517534
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Yuh-Man Sun

Masaryk University - Department of Biology ( email )

Czech Republic

Hana Hribkova

Masaryk University - Department of Biology ( email )

Czech Republic

Ibrahim Akkouh

University of Oslo - NORMENT ( email )

Norway

Marta Grabiec

Masaryk University - Department of Biology ( email )

Czech Republic

Eva Budinska

Masaryk University - Bioinformatics in Translational Research ( email )

Czech Republic

Attila Szabo

University of Oslo - NORMENT ( email )

Norway

Tomas Kasparek

University Hospital Brno ( email )

Brno
Czech Republic

Srdjan Djurovic (Contact Author)

University of Oslo - Department of Medical Genetics ( email )

Norway

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