GFAP-independent inflammatory competence and trophic functions of astrocytes generated from murine embryonic stem cells

The directed generation of pure astrocyte cultures from pluripotent stem cells has proven difficult. Generation of defined pluripotent-stem-cell derived astrocytes would allow new approaches to the investigation of plasticity and heterogeneity of astrocytes. We here describe a two-step differentiation scheme resulting in the generation of murine embryonic stem cell (mESC) derived astrocytes (MEDA), as characterized by the upregulation of 19 astrocyte-associated mRNAs, and positive staining of most cells for GFAP (glial fibrillary acidic protein), aquaporin-4 or glutamine synthetase. The MEDA cultures could be cryopreserved, and they neither contained neuronal, nor microglial cells. They also did not react to the microglial stimulus lipopolysaccharide, while inflammatory activation by a complete cytokine mix (CCM) or its individual components (TNF-α, IL1-β, IFN-γ) was readily observed. MEDA, stimulated by CCM, became susceptible to CD95 ligand-induced apoptosis and produced NO and IL-6. This was preceded by NF-kB activation, and up-regulation of relevant mRNAs. Also GFAP-negative astrocytes were fully inflammation-competent. Neurotrophic support by MEDA was found to be independent of GFAP expression. In summary, we described here the generation and functional characterization of microglia-free murine astrocytes, displaying phenotypic heterogeneity as is commonly observed in brain astrocytes

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

aquaporin, IL-6, single cell, neuronal support, glutamine synthetase

Zitieren

ISO 690

KÜGLER, Philipp, Bettina BAUMANN, Bastian ZIMMER, Sascha KELLER, Andreas MARX, Suzanne KADEREIT, Marcel LEIST, 2012. GFAP-independent inflammatory competence and trophic functions of astrocytes generated from murine embryonic stem cells. In: Glia. 2012, 60(2), pp. 218-228. ISSN 0894-1491. eISSN 1098-1136. Available under: doi: 10.1002/glia.21257

BibTex

@article{Kugler2012-02GFAPi-17413,
  year={2012},
  doi={10.1002/glia.21257},
  title={GFAP-independent inflammatory competence and trophic functions of astrocytes generated from murine embryonic stem cells},
  number={2},
  volume={60},
  issn={0894-1491},
  journal={Glia},
  pages={218--228},
  author={Kügler, Philipp and Baumann, Bettina and Zimmer, Bastian and Keller, Sascha and Marx, Andreas and Kadereit, Suzanne and Leist, Marcel}
}

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Universitätsbibliographie

Ja