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

Robert A. Bradley; Jack Shireman; Caya McFalls; Jeea Choi; Scott G. Canfield; Yi Dong; Katie Liu; Brianne Lisota; Jeffery R. Jones; Andrew Petersen; Anita Bhattacharyya; Sean P. Palecek; Eric V. Shusta; Christina Kendziorski; Su Chun Zhang

doi:10.1242/dev.170910

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

Robert A. Bradley
, Jack Shireman
, Caya McFalls
, Jeea Choi
, Scott G. Canfield
, Yi Dong
, Katie Liu
, Brianne Lisota
, Jeffery R. Jones
, Andrew Petersen
, Anita Bhattacharyya
, Sean P. Palecek
, Eric V. Shusta
, Christina Kendziorski
, Su Chun Zhang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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.

Original language	English
Article number	dev170910
Journal	Development (Cambridge)
Volume	146
Issue number	13
DOIs	https://doi.org/10.1242/dev.170910
State	Published - Jul 2019
Externally published	Yes

Keywords

Astrocyte heterogeneity
Blood-brain barrier
Human astrocyte development
Neuron-glia interaction
RNA-seq

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10.1242/dev.170910

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Bradley, R. A., Shireman, J., McFalls, C., Choi, J., Canfield, S. G., Dong, Y., Liu, K., Lisota, B., Jones, J. R., Petersen, A., Bhattacharyya, A., Palecek, S. P., Shusta, E. V., Kendziorski, C., & Zhang, S. C. (2019). Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties. Development (Cambridge), 146(13), Article dev170910. https://doi.org/10.1242/dev.170910

@article{09f820e72b154a8faeecf5b122184158,

title = "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.",

keywords = "Astrocyte heterogeneity, Blood-brain barrier, Human astrocyte development, Neuron-glia interaction, RNA-seq",

author = "Bradley, \{Robert A.\} and Jack Shireman and Caya McFalls and Jeea Choi and Canfield, \{Scott G.\} and Yi Dong and Katie Liu and Brianne Lisota and Jones, \{Jeffery R.\} and Andrew Petersen and Anita Bhattacharyya and Palecek, \{Sean P.\} and Shusta, \{Eric V.\} and Christina Kendziorski and Zhang, \{Su Chun\}",

note = "Publisher Copyright: {\textcopyright} 2019. Published by The Company of Biologists Ltd.",

year = "2019",

month = jul,

doi = "10.1242/dev.170910",

language = "英语",

volume = "146",

journal = "Development (Cambridge)",

issn = "0950-1991",

publisher = "Company of Biologists Ltd",

number = "13",

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Bradley, RA, Shireman, J, McFalls, C, Choi, J, Canfield, SG, Dong, Y, Liu, K, Lisota, B, Jones, JR, Petersen, A, Bhattacharyya, A, Palecek, SP, Shusta, EV, Kendziorski, C & Zhang, SC 2019, 'Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties', Development (Cambridge), vol. 146, no. 13, dev170910. https://doi.org/10.1242/dev.170910

TY - JOUR

T1 - Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties

AU - Bradley, Robert A.

AU - Shireman, Jack

AU - McFalls, Caya

AU - Choi, Jeea

AU - Canfield, Scott G.

AU - Dong, Yi

AU - Liu, Katie

AU - Lisota, Brianne

AU - Jones, Jeffery R.

AU - Petersen, Andrew

AU - Bhattacharyya, Anita

AU - Palecek, Sean P.

AU - Shusta, Eric V.

AU - Kendziorski, Christina

AU - Zhang, Su Chun

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

KW - Astrocyte heterogeneity

KW - Blood-brain barrier

KW - Human astrocyte development

KW - Neuron-glia interaction

KW - RNA-seq

UR - https://www.scopus.com/pages/publications/85069297228

U2 - 10.1242/dev.170910

DO - 10.1242/dev.170910

M3 - 文章

C2 - 31189664

AN - SCOPUS:85069297228

SN - 0950-1991

VL - 146

JO - Development (Cambridge)

JF - Development (Cambridge)

IS - 13

M1 - dev170910

ER -

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

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Keywords

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