The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes

Author:

Balint Vanda1,Peric Mina1,Dacic Sanja2ORCID,Stanisavljevic Ninkovic Danijela1ORCID,Marjanovic Jelena1,Popovic Jelena1,Stevanovic Milena123ORCID,Lazic Andrijana1

Affiliation:

1. Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, Serbia

2. Institute of Physiology and Biochemistry “Ivan Djaja”, Faculty of Biology, University of Belgrade, Studentski trg 16, 11158 Belgrade, Serbia

3. Serbian Academy of Sciences and Arts, Kneza Mihaila 35, 11001 Belgrade, Serbia

Abstract

Astrocytes are the main homeostatic cells in the central nervous system, with the unique ability to transform from quiescent into a reactive state in response to pathological conditions by reacquiring some precursor properties. This process is known as reactive astrogliosis, a compensatory response that mediates tissue damage and recovery. Although it is well known that SOX transcription factors drive the expression of phenotype-specific genetic programs during neurodevelopment, their roles in mature astrocytes have not been studied extensively. We focused on the transcription factors SOX2 and SOX9, shown to be re-expressed in reactive astrocytes, in order to study the reactivation-related functional properties of astrocytes mediated by those proteins. We performed an initial screening of SOX2 and SOX9 expression after sensorimotor cortex ablation injury in rats and conducted gain-of-function studies in vitro using astrocytes derived from the human NT2/D1 cell line. Our results revealed the direct involvement of SOX2 in the reacquisition of proliferation in mature NT2/D1-derived astrocytes, while SOX9 overexpression increased migratory potential and glutamate uptake in these cells. Our results imply that modulation of SOX gene expression may change the functional properties of astrocytes, which holds promise for the discovery of potential therapeutic targets in the development of novel strategies for tissue regeneration and recovery.

Funder

Ministry of Science, Technological Development and Innovation of the Republic of Serbia

Serbian Academy of Sciences and Arts

Publisher

MDPI AG

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