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

被引:0
作者
Szeky, Balazs [1 ]
Jurakova, Veronika [2 ]
Fouskova, Eliska [3 ]
Feher, Anita [1 ]
Zana, Melinda [1 ]
Karl, Vivien Reka [1 ]
Farkas, Janos [1 ]
Bodi-Jakus, Maria [1 ]
Zapletalova, Martina [2 ]
Pandey, Shashank [3 ]
Kucera, Radek [3 ,4 ]
Lochman, Jan [2 ,5 ]
Dinnyes, Andras [1 ,6 ]
机构
[1] BioTalentum Ltd, Godollo, Hungary
[2] Masaryk Univ, Fac Sci, Dept Biochem, Brno, Czech Republic
[3] Charles Univ Prague, Fac Med Pilsen, Dept Pharmacol & Toxicol, Plzen, Czech Republic
[4] Univ Hosp Plzen, Dept Immunochem Diagnost, Plzen, Czech Republic
[5] Czech Acad Sci, Inst Anim Physiol & Genet, Lab Neurobiol & Pathol Physiol, Brno, Czech Republic
[6] Hungarian Univ Agr & Life Sci, Inst Physiol & Anim Nutr, Dept Physiol & Anim Hlth, Godollo, Hungary
关键词
NEURAL PROGENITOR CELLS; CENTRAL-NERVOUS-SYSTEM; DIFFERENTIATION; OSCILLATIONS; EXPRESSION; CONVERSION; NEURONS; DISEASE;
D O I
10.1371/journal.pone.0313514
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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