Efficient derivation of functional astrocytes from human induced pluripotent stem cells (hiPSCs)

• Published in: PloS one 2024-12, Vol.19 (12), p.e0313514
• Main Authors: Szeky, Balazs, Jurakova, Veronika, Fouskova, Eliska, Feher, Anita, Zana, Melinda, Karl, Vivien Reka, Farkas, Janos, Bodi-Jakus, Maria, Zapletalova, Martina, Pandey, Shashank, Kucera, Radek, Lochman, Jan, Dinnyes, Andras
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyotrophic lateral sclerosis; Analysis; Antibodies; Aquaporin 4; Aquaporin 4 - metabolism; Astrocytes; Astrocytes - cytology; Astrocytes - metabolism; Biology and Life Sciences; Blood-brain barrier; Brain; Cell Differentiation; Cells, Cultured; Central nervous system; Cytokines - metabolism; Gene expression; Glial cells; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Health aspects; Homeostasis; Humans; Huntingtons disease; Immunology; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Inflammation; Lymphocytes; Medicine and Health Sciences; Microglia; Morphology; Neurodegenerative diseases; Neuronal-glial interactions; Neurons; Neurophysiology; Parkinson's disease; Pathogenesis; Pericytes; Pluripotency; Proteins; Research and Analysis Methods; S100 Calcium Binding Protein beta Subunit - metabolism; S100b protein; Stem cells; Synapses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0313514

Astrocytes are specialized glial cell types of the central nervous system (CNS) with remarkably high abundance, morphological and functional diversity. Astrocytes maintain neural metabolic support, synapse regulation, blood-brain barrier integrity and immunological homeostasis through intricate interactions with other cells, including neurons, microglia, pericytes and lymphocytes. Due to their extensive intercellular crosstalks, astrocytes are also implicated in the pathogenesis of CNS disorders, such as ALS (amyotrophic lateral sclerosis), Parkinson's disease and Alzheimer's disease. Despite the critical importance of astrocytes in neurodegeneration and neuroinflammation are recognized, the lack of suitable in vitro systems limits their availability for modeling human brain pathologies. Here, we report the time-efficient, reproducible generation of astrocytes from human induced pluripotent stem cells (hiPSCs). Our hiPSC-derived astrocytes expressed characteristic astrocyte markers, such as GFAP, S100b, ALDH1L1 and AQP4. Furthermore, hiPSC-derived astrocytes displayed spontaneous calcium transients and responded to inflammatory stimuli by the secretion of type A1 and type A2 astrocyte-related cytokines.