Isolation and transcriptional characterization of mouse perivascular astrocytes.

In the post-natal mammalian brain perivascular astrocytes (PAs) ensheath blood vessels to regulate their unique permeability properties known as the blood-brain barrier (BBB). Very little is known about PA-expressed genes and signaling pathways that mediate contact and communication with endothelial...

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Main Authors: Nejla Yosef, Yuanxin Xi, Joseph H McCarty
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0240035
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author Nejla Yosef
Yuanxin Xi
Joseph H McCarty
author_facet Nejla Yosef
Yuanxin Xi
Joseph H McCarty
author_sort Nejla Yosef
collection DOAJ
description In the post-natal mammalian brain perivascular astrocytes (PAs) ensheath blood vessels to regulate their unique permeability properties known as the blood-brain barrier (BBB). Very little is known about PA-expressed genes and signaling pathways that mediate contact and communication with endothelial cells (ECs) to regulate BBB physiology. This is due, in part, to lack of suitable models to distinguish PAs from other astrocyte sub-populations in the brain. To decipher the unique biology of PAs, we used in vivo gene knock-in technology to fluorescently label these cells in the adult mouse brain followed by fractionation and quantitative single cell RNA sequencing. In addition, PAs and non-PAs were also distinguished with transgenic fluorescent reporters followed by gene expression comparisons using bulk RNA sequencing. These efforts have identified several genes and pathways in PAs with potential roles in contact and communication with brain ECs. These genes encode various extracellular matrix (ECM) proteins and adhesion receptors, secreted growth factors, and intracellular signaling enzymes. Collectively, our experimental data reveal a set of genes that are expressed in PAs with putative roles in BBB physiology.
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spelling doaj.art-0bf49b6caae8401f9426c2cc1c9d10b92022-12-21T19:09:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011510e024003510.1371/journal.pone.0240035Isolation and transcriptional characterization of mouse perivascular astrocytes.Nejla YosefYuanxin XiJoseph H McCartyIn the post-natal mammalian brain perivascular astrocytes (PAs) ensheath blood vessels to regulate their unique permeability properties known as the blood-brain barrier (BBB). Very little is known about PA-expressed genes and signaling pathways that mediate contact and communication with endothelial cells (ECs) to regulate BBB physiology. This is due, in part, to lack of suitable models to distinguish PAs from other astrocyte sub-populations in the brain. To decipher the unique biology of PAs, we used in vivo gene knock-in technology to fluorescently label these cells in the adult mouse brain followed by fractionation and quantitative single cell RNA sequencing. In addition, PAs and non-PAs were also distinguished with transgenic fluorescent reporters followed by gene expression comparisons using bulk RNA sequencing. These efforts have identified several genes and pathways in PAs with potential roles in contact and communication with brain ECs. These genes encode various extracellular matrix (ECM) proteins and adhesion receptors, secreted growth factors, and intracellular signaling enzymes. Collectively, our experimental data reveal a set of genes that are expressed in PAs with putative roles in BBB physiology.https://doi.org/10.1371/journal.pone.0240035
spellingShingle Nejla Yosef
Yuanxin Xi
Joseph H McCarty
Isolation and transcriptional characterization of mouse perivascular astrocytes.
PLoS ONE
title Isolation and transcriptional characterization of mouse perivascular astrocytes.
title_full Isolation and transcriptional characterization of mouse perivascular astrocytes.
title_fullStr Isolation and transcriptional characterization of mouse perivascular astrocytes.
title_full_unstemmed Isolation and transcriptional characterization of mouse perivascular astrocytes.
title_short Isolation and transcriptional characterization of mouse perivascular astrocytes.
title_sort isolation and transcriptional characterization of mouse perivascular astrocytes
url https://doi.org/10.1371/journal.pone.0240035
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