TY - JOUR
T1 - NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates
AU - Boghdadi, Anthony G.
AU - Spurrier, Joshua
AU - Teo, Leon
AU - Li, Mingfeng
AU - Skarica, Mario
AU - Cao, Benjamin
AU - Kwan, William C.
AU - Merson, Tobias D.
AU - Nilsson, Susan K.
AU - Sestan, Nenad
AU - Strittmatter, Stephen M.
AU - Bourne, James A.
N1 - Funding Information:
The authors wish to acknowledge the technical assistance and contributions of A.L. Chan, A. Grubman, J. Legrand, A.M. Tichy, M. de Souza, T.A. Hoang, J. Homman-Ludiye, and C.G. Sobey. This work was supported by grants from the NHMRC (APP108197) to J.A.B. at Monash University, and from the NIH (R35 NS097283) and the Falk Medical Research Trust to S.M.S. at Yale University. A NHMRC Senior Research Fellowship (APP1077677) supports J.A.B. An Australian Postgraduate Award Scholarship supports A.G.B. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85119824848&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-27245-0
DO - 10.1038/s41467-021-27245-0
M3 - Article
C2 - 34824275
AN - SCOPUS:85119824848
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6906
ER -