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

Author:

Bradley Robert A.12ORCID,Shireman Jack1,McFalls Caya1,Choi Jeea3,Canfield Scott G.45,Dong Yi1,Liu Katie1,Lisota Brianne1,Jones Jeffery R.1,Petersen Andrew1,Bhattacharyya Anita1,Palecek Sean P.4,Shusta Eric V.4,Kendziorski Christina6,Zhang Su-Chun1278ORCID

Affiliation:

1. 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. 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, Department of Neurology, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, WI 53705, USA

8. Program in Neuroscience & Behavioral Disorders, Duke-NUS Medical School, Singapore

Abstract

Astrocytes display diverse morphologies in different regions of the central nervous system. Whether astrocyte diversity is attributable to developmental processes and bears functional consequence, especially in humans, is unknown. RNA sequencing 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.

Funder

National Institutes of Health

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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