ABSTRACT
The original version of this Article contained an error in Fig. 1, in which a number of incorrect fluorescence images were inadvertently incorporated into the panel. This has been corrected in both the PDF and HTML versions of the Article.
ABSTRACT
The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs). All astrocytes expressed functional markers including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter-1 (EAAT1), S100B and glutamine synthetase (GS) comparable to that of adult astrocytes in vivo. However, induced astrocytes derived from both SAD and FAD patients exhibit a pronounced pathological phenotype, with a significantly less complex morphological appearance, overall atrophic profiles and abnormal localisation of key functional astroglial markers. Furthermore, NPCs derived from identical patients did not show any differences, therefore, validating that remodelled astroglia are not as a result of defective neural intermediates. This work not only presents a novel model to study the mechanisms of human astrocytes in vitro, but also provides an ideal platform for further interrogation of early astroglial cell autonomous events in AD and the possibility of identification of novel therapeutic targets for the treatment of AD.
Subject(s)
Alzheimer Disease/pathology , Astrocytes/pathology , Induced Pluripotent Stem Cells/pathology , Alzheimer Disease/metabolism , Astrocytes/metabolism , Atrophy/metabolism , Atrophy/pathology , Biomarkers/metabolism , Cell Differentiation/physiology , Cells, Cultured , Excitatory Amino Acid Transporter 1/metabolism , Glial Fibrillary Acidic Protein/metabolism , Glutamate-Ammonia Ligase/metabolism , Humans , Induced Pluripotent Stem Cells/metabolism , Male , Middle Aged , Neural Stem Cells/metabolism , Neural Stem Cells/pathology , S100 Calcium Binding Protein beta Subunit/metabolism , Stem Cells/metabolism , Stem Cells/physiology , Up-Regulation/physiologyABSTRACT
The continuous advancements in cancer research have contributed to the overwhelming evidence of the presence of telomerase in primary and secondary tumours together with hsp90 and c-Myc. This review will discuss the important role of telomerase together with hsp90 and c-Myc within the initiation and progression of gliomas. Also it will review the differential expression of these genes in the different grades of gliomas and the possibility of new treatments targeting these specific genes.
