Universität zu Köln

Kleiderman, Susanne, Sa, Joao V., Teixeira, Ana P., Brito, Catarina ORCID: 0000-0002-8926-279X, Gutbier, Simon, Evje, Lars G., Hadera, Mussie G., Glaab, Enrico ORCID: 0000-0003-3977-7469, Henry, Margit, Sachinidis, Agapios, Alves, Paula M., Sonnewald, Ursula and Leist, Marcel ORCID: 0000-0002-3778-8693 (2016). Functional and phenotypic differences of pure populations of stem cell-derived astrocytes and neuronal precursor cells. Glia, 64 (5). S. 695 - 716. HOBOKEN: WILEY. ISSN 1098-1136

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Abstract

Availability of homogeneous astrocyte populations would facilitate research concerning cell plasticity (metabolic and transcriptional adaptations; innate immune responses) and cell cycle reactivation. Current protocols to prepare astrocyte cultures differ in their final content of immature precursor cells, preactivated cells or entirely different cell types. A new method taking care of all these issues would improve research on astrocyte functions. We found here that the exposure of a defined population of pluripotent stem cell-derived neural stem cells (NSC) to BMP4 results in pure, nonproliferating astrocyte cultures within 24-48 h. These murine astrocytes generated from embryonic stem cells (mAGES) expressed the positive markers GFAP, aquaporin 4 and GLT-1, supported neuronal function, and acquired innate immune functions such as the response to tumor necrosis factor and interleukin 1. The protocol was applicable to several normal or disease-prone pluripotent cell lines, and the corresponding mAGES all exited the cell cycle and lost most of their nestin expression, in contrast to astrocytes generated by serum-addition or obtained as primary cultures. Comparative gene expression analysis of mAGES and NSC allowed quantification of differences between the two cell types and a definition of an improved marker set to define astrocytes. Inclusion of several published data sets in this transcriptome comparison revealed the similarity of mAGES with cortical astrocytes in vivo. Metabolic analysis of homogeneous NSC and astrocyte populations revealed distinct neurochemical features: both cell types synthesized glutamine and citrate, but only mature astrocytes released these metabolites. Thus, the homogeneous cultures allowed an improved definition of NSC and astrocyte features. GLIA 2016;64:695-715

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kleiderman, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Sa, Joao V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Teixeira, Ana P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brito, Catarina UNSPECIFIED orcid.org/0000-0002-8926-279X UNSPECIFIED Gutbier, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Evje, Lars G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hadera, Mussie G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Glaab, Enrico UNSPECIFIED orcid.org/0000-0003-3977-7469 UNSPECIFIED Henry, Margit UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Alves, Paula M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sonnewald, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Leist, Marcel UNSPECIFIED orcid.org/0000-0002-3778-8693 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-277669
DOI:	10.1002/glia.22954
Journal or Publication Title:	Glia
Volume:	64
Number:	5
Page Range:	S. 695 - 716
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1098-1136
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FIBRILLARY ACIDIC PROTEIN; CENTRAL-NERVOUS-SYSTEM; NEURAL STEM; DEVELOPMENTAL NEUROTOXICITY; GLUTAMINE-SYNTHETASE; ASTROGLIAL CULTURES; RADIAL GLIA; EXPRESSION; DIFFERENTIATION; METABOLISM Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27766