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P3‐160: PROGENITOR RESERVE HYPOTHESIS: A MODEL FOR DISCOVERING PROTECTIVE FACTORS IN OLDER ADULTS AT RISK FOR DEMENTIA
Author(s) -
Nation Daniel A.,
Tan Alick,
McIntosh Elissa C.,
Dutt Shubir,
Ho Jean K.,
Jang Jung,
Yew Belinda,
Rodgers Kathleen E.,
Brickman Adam M.,
Meier Irene,
Chang Katherine,
Blanken Anna E.,
Gaubert Aimee
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.1518
Subject(s) - cerebral amyloid angiopathy , dementia , atrophy , medicine , pathology , cerebral blood flow , hyperintensity , psychology , magnetic resonance imaging , disease , radiology
of primary human astrocytes, human iPSCs are currently used as a source of astrocytes. However, existing methods for astrocyte generation are slow (up to 6 months) or require additional selection to reduce heterogeneity. Methods: To rapidly generate mature astrocytes for disease modeling, we have developed a novel protocol that uses inducible expression of astrocyte differentiation master transcription factors NFIA and SOX9 and an optimized astrocyte differentiation medium. Results: Human cortical or spinal astrocytes can be generated from normal or disease iPSCs in only one month. They express the key astrocyte markers GFAP and S100b at >90% and exhibit mature process-bearing morphologies. These astrocytes can promote neuron synapse formation and functional activity in MEA and calcium imaging applications, and elicit a strong and rapid pro-inflammatory response. Conclusions:This protocol represents an important tool for modeling neurological diseases using a human iPSC-based astrocyte-neuron coculture platform, allowing the role of diseased astrocytes in neuronal degeneration to be probed.