Reactive astrogliosis in the era of single-cell transcriptomics

Front Cell Neurosci. 2023 Apr 20:17:1173200. doi: 10.3389/fncel.2023.1173200. eCollection 2023.

Abstract

Reactive astrogliosis is a reaction of astrocytes to disturbed homeostasis in the central nervous system (CNS), accompanied by changes in astrocyte numbers, morphology, and function. Reactive astrocytes are important in the onset and progression of many neuropathologies, such as neurotrauma, stroke, and neurodegenerative diseases. Single-cell transcriptomics has revealed remarkable heterogeneity of reactive astrocytes, indicating their multifaceted functions in a whole spectrum of neuropathologies, with important temporal and spatial resolution, both in the brain and in the spinal cord. Interestingly, transcriptomic signatures of reactive astrocytes partially overlap between neurological diseases, suggesting shared and unique gene expression patterns in response to individual neuropathologies. In the era of single-cell transcriptomics, the number of new datasets steeply increases, and they often benefit from comparisons and integration with previously published work. Here, we provide an overview of reactive astrocyte populations defined by single-cell or single-nucleus transcriptomics across multiple neuropathologies, attempting to facilitate the search for relevant reference points and to improve the interpretability of new datasets containing cells with signatures of reactive astrocytes.

Keywords: CNS diseases; astrocytes; cell populations; neurodegeneration; neuroinflammation; reactive astrogliosis; single-cell RNA-seq.

Publication types

  • Review

Grants and funding

LV, ZM, and MK have been supported by the Ministry of Education, Youth, and Sports, under the frame of EJP RD, the European Joint Programme on Rare Diseases: CZ.1.05/1.1.00/02.0109, RVO 86652036, the European Union's Horizon 2020 research and innovation program under the EJP RD COFUND- EJP N° 825575, Czech Science Foundation GACR 23-05327S and 23-06269S, and project LX22NPO5107 (MEYS): Financed by EU—Next Generation EU. EH has been supported by grants from Alzheimer Nederland (WE.03-2017-4), NWO Gravitation BRAINSCAPES (463002004), ZonMW Memorabel (733050816), ZonMW TOP (91217035), EJP RD ALEXANDER (JTC2019/ZonMW 463002004), and la Caixa Foundation LCF/PR/HR21/52410002 (Astromad). MP has been supported by the grants from Swedish Research Council (2017-02255, 2019-00284, and 2020-01148), the ALF (724421 and 965939), W. and M. Lundgren's Foundation, The Swedish Brain Foundation (FO2018-0252 and FO2021-0082), The Swedish Stroke Foundation, Hagströmer's Foundation Millennium, T. Söderberg's Foundations, la Caixa Foundation LCF/PR/HR21/52410002 (Astromad), and P. Eriksson's, E. Jacobson's, R., and U. Amlöv's Foundations.