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

Development. 2019 Jul 8;146(13):dev170910. doi: 10.1242/dev.170910.

Authors

Robert A Bradley^{1

2}, Jack Shireman¹, Caya McFalls¹, Jeea Choi³, Scott G Canfield^{4

5}, Yi Dong¹, Katie Liu¹, Brianne Lisota¹, Jeffery R Jones¹, Andrew Petersen¹, Anita Bhattacharyya¹, Sean P Palecek⁴, Eric V Shusta⁴, Christina Kendziorski⁶, Su-Chun Zhang^{7

2

8

9}

Affiliations

¹ Department of Neuroscience, Waisman Center, University of Wisconsin - Madison, Madison, WI 53705, USA.
² Cellular and Molecular Biology Program, University of Wisconsin - Madison, Madison, WI 53705, USA.
³ Department of Statistics, University of Wisconsin - Madison, Madison, WI 53705, USA.
⁴ Department of Chemical and Biological Engineering, University of Wisconsin - Madison, Madison, WI 53705, USA.
⁵ Department of Cellular and Integrative Physiology, School of Medicine, Indiana University - Terre Haute, IN 47885, USA.
⁶ Department of Biostatistics and Medical Informatics, University of Wisconsin - Madison, Madison, WI 53792, USA.
⁷ Department of Neuroscience, Waisman Center, University of Wisconsin - Madison, Madison, WI 53705, USA [email protected].
⁸ Department of Neuroscience, Department of Neurology, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, WI 53705, USA.
⁹ Program in Neuroscience & Behavioral Disorders, Duke-NUS Medical School, Singapore 169857.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Astrocytes / physiology*
Base Sequence
Biomarkers / analysis
Biomarkers / metabolism
Cell Differentiation / genetics*
Cells, Cultured
Cerebral Cortex / cytology
Cerebral Cortex / metabolism
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
Humans
Induced Pluripotent Stem Cells / physiology
Neural Stem Cells / physiology
Neurogenesis / genetics*
Organ Specificity / genetics
Pluripotent Stem Cells / physiology*
Prosencephalon / cytology
Prosencephalon / metabolism
Sequence Analysis, RNA
Transcriptome*

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding