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Method Article
Rapid and Efficient Induction of Functional Astrocytes from Human Pluripotent Stem Cells
Henrik Ahlenius
Lund Stem Cell Center
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Current protocols for differentiation of human pluripotent stem cells to astrocytes are slow and inefficient, and characterization of the generated cells is incomplete. These shortcomings severely limit research on the biology of human astrocytes and their involvement in neurological disorders.
Here we capitalized on recent transcription factor-driven methods to develop a novel protocol for astrocyte differentiation. We demonstrate that overexpression of two gliogenic transcription factors, Sox9 and Nfib, in human pluripotent stem cells rapidly and efficiently gives rise to a highly homogenous population of astrocytes as early as 7 days post-transduction. After 14 days, these induced astrocytes (iAs) exhibit molecular signatures and functional properties closely resembling those of adult human astrocytes. The iAs also recapitulate disease phenotype in a genome-engineered model of Alexander disease.
Our approach provides an easy, time-efficient, effective and scalable method that will provide new opportunities for studies on the role of human astrocytes in health and disease.
Keywords
human astrocyte, stem cells, differentiation
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This is a preprint. It has not completed peer review.
Method Article
Rapid and Efficient Induction of Functional Astrocytes from Human Pluripotent Stem Cells
Henrik Ahlenius
Lund Stem Cell Center
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 20 Aug, 2018
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Current protocols for differentiation of human pluripotent stem cells to astrocytes are slow and inefficient, and characterization of the generated cells is incomplete. These shortcomings severely limit research on the biology of human astrocytes and their involvement in neurological disorders.
Here we capitalized on recent transcription factor-driven methods to develop a novel protocol for astrocyte differentiation. We demonstrate that overexpression of two gliogenic transcription factors, Sox9 and Nfib, in human pluripotent stem cells rapidly and efficiently gives rise to a highly homogenous population of astrocytes as early as 7 days post-transduction. After 14 days, these induced astrocytes (iAs) exhibit molecular signatures and functional properties closely resembling those of adult human astrocytes. The iAs also recapitulate disease phenotype in a genome-engineered model of Alexander disease.
Our approach provides an easy, time-efficient, effective and scalable method that will provide new opportunities for studies on the role of human astrocytes in health and disease.