Dataset Information

Isolation and transcriptional characterization of mouse perivascular astrocytes.

ABSTRACT: 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.

SUBMITTER: Yosef N

PROVIDER: S-EPMC7544046 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Isolation and transcriptional characterization of mouse perivascular astrocytes.

Yosef Nejla N Xi Yuanxin Y McCarty Joseph H JH

PloS one 20201008 10

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, w ...[more]

PMID: 33031376

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Project description:UnlabelledReactive gliosis involving activation and proliferation of astrocytes and microglia, is a widespread but largely complex and graded glial response to brain injury. Astroglial population has a previously underestimated high heterogeneity with cells differing in their morphology, gene expression profile, and response to injury. Here, we identified a subset of reactive astrocytes isolated from brain focal ischemic lesions that show several atypical characteristics. Ischemia-derived astrocytes (IDAs) were isolated from early ischemic penumbra and core. IDA did not originate from myeloid precursors, but rather from pre-existing local progenitors. Isolated IDA markedly differ from primary astrocytes, as they proliferate in vitro with high cell division rate, show increased migratory ability, have reduced replicative senescence and grow in the presence of macrophages within the limits imposed by the glial scar. Remarkably, IDA produce a conditioned medium that strongly induced activation on quiescent primary astrocytes and potentiated the neuronal death triggered by oxygen-glucose deprivation. When re-implanted into normal rat brains, eGFP-IDA migrated around the injection site and induced focal reactive gliosis. Inhibition of gamma secretases or culture on quiescent primary astrocytes monolayers facilitated IDA differentiation to astrocytes. We propose that IDA represent an undifferentiated, pro-inflammatory, highly replicative and migratory astroglial subtype emerging from the ischemic microenvironment that may contribute to the expansion of reactive gliosis.Main pointsIschemia-derived astrocytes (IDA) were isolated from brain ischemic tissue IDA show reduced replicative senescence, increased cell division and spontaneous migration IDA potentiate death of oxygen-glucose deprived cortical neurons IDA propagate reactive gliosis on quiescent astrocytes in vitro and in vivo Inhibition of gamma secretases facilitates IDA differentiation to astrocytes.

Dataset Information

Isolation and transcriptional characterization of mouse perivascular astrocytes.

Publications

Isolation and transcriptional characterization of mouse perivascular astrocytes.

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