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NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates

Author

Listed:
  • Anthony G. Boghdadi

    (Monash University)

  • Joshua Spurrier

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine)

  • Leon Teo

    (Monash University)

  • Mingfeng Li

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Mario Skarica

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Benjamin Cao

    (Monash University
    Biomedical Manufacturing CSIRO Manufacturing)

  • William C. Kwan

    (Monash University)

  • Tobias D. Merson

    (Monash University)

  • Susan K. Nilsson

    (Monash University
    Biomedical Manufacturing CSIRO Manufacturing)

  • Nenad Sestan

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine)

  • Stephen M. Strittmatter

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine)

  • James A. Bourne

    (Monash University)

Abstract

Astrocytes play critical roles after brain injury, but their precise function is poorly defined. Utilizing single-nuclei transcriptomics to characterize astrocytes after ischemic stroke in the visual cortex of the marmoset monkey, we observed nearly complete segregation between stroke and control astrocyte clusters. Screening for the top 30 differentially expressed genes that might limit stroke recovery, we discovered that a majority of astrocytes expressed RTN4A/ NogoA, a neurite-outgrowth inhibitory protein previously only associated with oligodendrocytes. NogoA upregulation on reactive astrocytes post-stroke was significant in both the marmoset and human brain, whereas only a marginal change was observed in mice. We determined that NogoA mediated an anti-inflammatory response which likely contributes to limiting the infiltration of peripheral macrophages into the surviving parenchyma.

Suggested Citation

  • Anthony G. Boghdadi & Joshua Spurrier & Leon Teo & Mingfeng Li & Mario Skarica & Benjamin Cao & William C. Kwan & Tobias D. Merson & Susan K. Nilsson & Nenad Sestan & Stephen M. Strittmatter & James A, 2021. "NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27245-0
    DOI: 10.1038/s41467-021-27245-0
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    References listed on IDEAS

    as
    1. Maio S. Chen & Andrea B. Huber & Marjan E. van der Haar & Marcus Frank & Lisa Schnell & Adrian A. Spillmann & Franziska Christ & Martin E. Schwab, 2000. "Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1," Nature, Nature, vol. 403(6768), pages 434-439, January.
    2. Tadzia GrandPré & Fumio Nakamura & Timothy Vartanian & Stephen M. Strittmatter, 2000. "Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein," Nature, Nature, vol. 403(6768), pages 439-444, January.
    3. Fenna M. Krienen & Melissa Goldman & Qiangge Zhang & Ricardo C. H. Rosario & Marta Florio & Robert Machold & Arpiar Saunders & Kirsten Levandowski & Heather Zaniewski & Benjamin Schuman & Carolyn Wu &, 2020. "Author Correction: Innovations present in the primate interneuron repertoire," Nature, Nature, vol. 588(7837), pages 17-17, December.
    4. Fenna M. Krienen & Melissa Goldman & Qiangge Zhang & Ricardo del Rosario & Marta Florio & Robert Machold & Arpiar Saunders & Kirsten Levandowski & Heather Zaniewski & Benjamin Schuman & Carolyn Wu & A, 2020. "Innovations present in the primate interneuron repertoire," Nature, Nature, vol. 586(7828), pages 262-269, October.
    5. Shane A. Liddelow & Kevin A. Guttenplan & Laura E. Clarke & Frederick C. Bennett & Christopher J. Bohlen & Lucas Schirmer & Mariko L. Bennett & Alexandra E. Münch & Won-Suk Chung & Todd C. Peterson & , 2017. "Neurotoxic reactive astrocytes are induced by activated microglia," Nature, Nature, vol. 541(7638), pages 481-487, January.
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    1. Daniel Bormann & Michael Knoflach & Emilia Poreba & Christian J. Riedl & Giulia Testa & Cyrille Orset & Anthony Levilly & Andréa Cottereau & Philipp Jauk & Simon Hametner & Nadine Stranzl & Bahar Gola, 2024. "Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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