Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways

Zhang, Sheng; Kim, Bokyung; Zhu, Xiaoqing; Gui, Xuehong; Wang, Yan; Lan, Zhaohui; Prabhu, Preeti; Fond, Kenneth; Wang, Aijun; Guo, Fuzheng

doi:10.1038/s41467-020-15656-4

Cited by 48 publications

(66 citation statements)

References 58 publications

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“…1a). We analyzed the spinal cord at postnatal day 14 (P14) because mGfap-Cre-mediated gene recombination is specific to astrocytes in the spinal cord and the recombination efficiency gradually reaches to ~80% by P14 (19). Consistently, SOX2 was ablated in ~84% of astrocytes labeled by brain lipid basic protein (BLBP) in the spinal cord of mGfap:Sox2 cKO mice at P14 (Fig.…”

Section: Sox2 Regulates Astroglial Molecular Maturation and Is Dispenmentioning

confidence: 99%

“…All mice were housed at 12 hours light/dark cycle with free access to food and drink. All transgenic mice were maintained on a C57BL/6 background and approved by Institutional IMSR_JAX:006148) were described in our previous studies (13,14,19). mTmG (RRID: IMSR_JAX:007676) mice were purchased from the Jackson Laboratory and described in previous study (22).…”

Section: Animals and Sox2 Conditional Knockout (Cko)mentioning

confidence: 99%

“…In our study, we referred to the mGfap-Cre:Sox2 fl/fl mice as mGfap:Sox2 cKO mice, Aldh1l1-CreER T2 :Sox2 fl/fl as Aldh1l1:Sox2 cKO mice. Both Aldh1l1(or Sox2)-CreER T2 :Sox2 fl/fl and corresponding non-Cre littermate mice (Sox2 fl/fl or Sox2 fl/+ ) were treated subcutaneously with tamoxifen (or hydroxytamoxifen, OH-TM) according to our previous protocolss (19).…”

Section: Animals and Sox2 Conditional Knockout (Cko)mentioning

confidence: 99%

“…The volume-rendered confocal images were subsequently imported to NIH ImageJ 1.46r for quantifying the percentage of astrcoyte marker occupying area among total area. We used a customer-defined Image J Macro program acoording to our previous protocol for semi-automated quantification (19). At least three sections from each mouse were used for ImageJ quantification.…”

Section: Astrocyte Morphology Analysismentioning

confidence: 99%

“…Tissue process, in situ hybridization, and immunohistochemistry were performed according to our previous protocols (19). A 614bp digoxinin-conjugated complementary RNA (cRNA) probe (targeting Gfap mRNA) was prepared using SP6 RNA polymerase-mediated in vitro transcription.…”

Section: Tissue Preparation In Situ Hybridization and Immunohistochmentioning

confidence: 99%

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The stem cell transcription factor SOX2 is essential for astrocyte maturation and controls animal hyperactive behavior

Zhang¹,

Lan²,

Wang³

et al. 2020

Preprint

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Children with SOX2-deficiency develop anophthalmia/microphthalmia and display neurological impairment. Here we report an essential role for astroglial SOX2 in brain anomalies and neurological defects. Sox2-deficiency inhibited postnatal astrocyte maturation without affecting astroglial proliferation and population expansion. Mechanistically, we found that SOX2 directly bound to a cohort of astrocytic signature genes such as those involving in glutamate transport and that Sox2-deficiency remarkably reduced glutamate transporter expression and compromised astrocyte function of glutamate uptake. Behaviorally, astroglial Sox2-deficient mice developed hyperactivity in locomotion while their motor skills, social capability, and learning abilities were unaffected. We found that astroglial Sox2-deficiency results in elevated glutamatergic synapse formation and elevated excitability of striatal medium spiny neurons, which has been shown to trigger hyperactive locomotion. Our study provides new insights into the biological mechanisms underlying brain defects in children with SOX2 mutations and unveils a novel connection between astrocyte SOX2 and brain development and behavior.

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Section: Sox2 Regulates Astroglial Molecular Maturation and Is Dispenmentioning

confidence: 99%

Section: Animals and Sox2 Conditional Knockout (Cko)mentioning

confidence: 99%

Section: Animals and Sox2 Conditional Knockout (Cko)mentioning

confidence: 99%

Section: Astrocyte Morphology Analysismentioning

confidence: 99%

Section: Tissue Preparation In Situ Hybridization and Immunohistochmentioning

confidence: 99%

See 3 more Smart Citations

The stem cell transcription factor SOX2 is essential for astrocyte maturation and controls animal hyperactive behavior

Zhang¹,

Lan²,

Wang³

et al. 2020

Preprint

Self Cite

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Bacteria‐Derived Outer‐Membrane Vesicles Hitchhike Neutrophils to Enhance Ischemic Stroke Therapy

et al. 2023

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The treatment of reperfusion injury after ischemic stroke remains unsatisfactory since the blood‐brain barrier (BBB) prevents most neuroprotective agents from entering the brain. Here, a strategy is proposed based on bacteria‐derived outer‐membrane vesicle (OMV) hitchhiking on the neutrophils for enhanced brain delivery of pioglitazone (PGZ) to treat ischemic stroke. By encapsulating PGZ into OMV, the resulting OMV@PGZ nanoparticles inherit the functions associated with the bacterial outer membrane, making them ideal decoys for neutrophil uptake. The results show that OMV@PGZ simultaneously inhibits the activation of nucleotide oligomerization‐like receptor protein 3 (NLRP3) inflammasomes and ferroptosis and reduces the reperfusion injury to exert a neuroprotective effect. Notably, the transcription factors Pou2f1 and Nrf1 of oligodendrocytes are identified for the first time to be involved in this process and promoted neural repair by single‐nucleus RNA sequencing (snRNA‐seq).

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How lung injury and therapeutic oxygen could alter white matter development

Dettman

Dizon

2021

J of Neuroscience Research

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Developmental brain injury describes a spectrum of neurological pathologies resulting from either antenatal or perinatal injury. This includes both cognitive and motor defects that affect patients for their entire lives. Developmental brain injury can be caused by a spectrum of conditions including stroke, perinatal hypoxia‐ischemia, and intracranial hemorrhage. Additional risk factors have been identified including very low birth weight, mechanical ventilation, and oxygen (O2) supplementation. In fact, infants with bronchopulmonary dysplasia, an inflammatory disease associated with disrupted lung development, have been shown to have decreased cerebral white matter and decreased intracranial volumes. Thus, there appears to be a developmental link between the lung, O2, and the brain that leads to proper myelination. Here, we will discuss what is currently known about the link between O2 and myelination and how scientists are exploring mechanisms through which supplemental O2 and/or lung injury can affect brain development. Consideration of a link between the diseased lung and developing brain will allow clinicians to fine tune their approaches in managing preterm lung disease in order to optimize brain health.

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Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways

Cited by 48 publications

References 58 publications

The stem cell transcription factor SOX2 is essential for astrocyte maturation and controls animal hyperactive behavior

The stem cell transcription factor SOX2 is essential for astrocyte maturation and controls animal hyperactive behavior

Bacteria‐Derived Outer‐Membrane Vesicles Hitchhike Neutrophils to Enhance Ischemic Stroke Therapy

How lung injury and therapeutic oxygen could alter white matter development

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