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Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties.


ABSTRACT: Astrocytes display diverse morphologies in different regions of the central nervous system. Whether astrocyte diversity is attributable to developmental processes and bears functional consequences, especially in humans, is unknown. RNA-seq of human pluripotent stem cell-derived regional astrocytes revealed distinct transcript profiles, suggesting differential functional properties. This was confirmed by differential calcium signaling as well as effects on neurite growth and blood-brain barrier formation. Distinct transcriptional profiles and functional properties of human astrocytes generated from regionally specified neural progenitors under the same conditions strongly implicate the developmental impact on astrocyte diversity. These findings provide a rationale for renewed examination of regional astrocytes and their role in the pathogenesis of psychiatric and neurological disorders.

SUBMITTER: Bradley RA 

PROVIDER: S-EPMC6633609 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties.

Bradley Robert A RA   Shireman Jack J   McFalls Caya C   Choi Jeea J   Canfield Scott G SG   Dong Yi Y   Liu Katie K   Lisota Brianne B   Jones Jeffery R JR   Petersen Andrew A   Bhattacharyya Anita A   Palecek Sean P SP   Shusta Eric V EV   Kendziorski Christina C   Zhang Su-Chun SC  

Development (Cambridge, England) 20190708 13


Astrocytes display diverse morphologies in different regions of the central nervous system. Whether astrocyte diversity is attributable to developmental processes and bears functional consequences, especially in humans, is unknown. RNA-seq of human pluripotent stem cell-derived regional astrocytes revealed distinct transcript profiles, suggesting differential functional properties. This was confirmed by differential calcium signaling as well as effects on neurite growth and blood-brain barrier f  ...[more]

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