Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans
Central nervous system (CNS)-border associated macrophages (BAMs) maintain their steady-state population during adulthood and are not replaced by circulating monocytes under physiological conditions. Their roles in CNS integrity and functions under pathological conditions remain largely unknown. Unt...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-04-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996119303973 |
| _version_ | 1818353321305440256 |
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| author | Wenson D. Rajan Bartosz Wojtas Bartlomiej Gielniewski Francesc Miró-Mur Jordi Pedragosa Malgorzata Zawadzka Paulina Pilanc Anna M. Planas Bozena Kaminska |
| author_facet | Wenson D. Rajan Bartosz Wojtas Bartlomiej Gielniewski Francesc Miró-Mur Jordi Pedragosa Malgorzata Zawadzka Paulina Pilanc Anna M. Planas Bozena Kaminska |
| author_sort | Wenson D. Rajan |
| collection | DOAJ |
| description | Central nervous system (CNS)-border associated macrophages (BAMs) maintain their steady-state population during adulthood and are not replaced by circulating monocytes under physiological conditions. Their roles in CNS integrity and functions under pathological conditions remain largely unknown. Until recently, BAMs and microglia could not be unequivocally distinguished due to expression of common macrophage markers. We investigated the transcriptional profiles of immunosorted BAMs from rat sham-operated and ischemic brains using RNA sequencing. We found that BAMs express the distinct transcriptional signature than microglia and infiltrating macrophages. The enrichment of functional groups associated with the cell cycle in CD163+ cells isolated 3 days after the ischemic injury indicates the proliferative capacity of these cells. The increased number of CD163+ cells 3 days post-ischemia was corroborated by flow cytometry and detecting the increased number of CD163+ cells positive for a proliferation marker Ki67 at perivascular spaces. CD163+ cells in the ischemic brains up-regulated many inflammatory genes and parenchymal CD163+ cells expressed iNOS, which indicates acquisition of a pro-inflammatory phenotype. In mice, BAMs typically express CD206 and we found a subset of these cells expressing CD169. Chimeric mice generated by transplanting bone marrow of donor Cx3cr1gfpCCR2rfp mice to wild type hosts showed an increased number of CX3CR1+CD169+ perivascular macrophages 3 days post-ischemia. Furthermore, these cells accumulated in the brain parenchyma and we detected replacement of perivascular macrophages by peripheral monocytic cells in the sub-acute phase of stroke. In line with the animal results, post-mortem brain samples from human ischemic stroke cases showed time-dependent accumulation of CD163+ cells in the ischemic parenchyma. Our findings indicate a unique transcriptional signature of BAMs, their local proliferation and migration of inflammatory BAMs to the brain parenchyma after stroke in animal models and humans. |
| first_indexed | 2024-12-13T19:07:40Z |
| format | Article |
| id | doaj.art-780649d76e204882895a69ff0ac3d302 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T19:07:40Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-780649d76e204882895a69ff0ac3d3022022-12-21T23:34:29ZengElsevierNeurobiology of Disease1095-953X2020-04-01137104722Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humansWenson D. Rajan0Bartosz Wojtas1Bartlomiej Gielniewski2Francesc Miró-Mur3Jordi Pedragosa4Malgorzata Zawadzka5Paulina Pilanc6Anna M. Planas7Bozena Kaminska8Nencki Institute of Experimental Biology, Polish Academy of Sciences, Laboratory of Molecular Neurobiology, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Laboratory of Molecular Neurobiology, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Laboratory of Molecular Neurobiology, Warsaw, PolandInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Àrea de Neurociències, Barcelona, SpainInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Àrea de Neurociències, Barcelona, SpainNencki Institute of Experimental Biology, Polish Academy of Sciences, Laboratory of Molecular Neurobiology, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Laboratory of Molecular Neurobiology, Warsaw, PolandInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Àrea de Neurociències, Barcelona, Spain; Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de InvestigacionesCientíficas (CSIC), Departament d'Isquèmia Cerebral I Neurodegeneració, Barcelona, SpainNencki Institute of Experimental Biology, Polish Academy of Sciences, Laboratory of Molecular Neurobiology, Warsaw, Poland; Corresponding author at: The Nencki Institute of Experimental Biology, Laboratory of Molecular Neurobiology, Neurobiology Center, 3 Pasteur Str., 02-093 Warsaw, Poland.Central nervous system (CNS)-border associated macrophages (BAMs) maintain their steady-state population during adulthood and are not replaced by circulating monocytes under physiological conditions. Their roles in CNS integrity and functions under pathological conditions remain largely unknown. Until recently, BAMs and microglia could not be unequivocally distinguished due to expression of common macrophage markers. We investigated the transcriptional profiles of immunosorted BAMs from rat sham-operated and ischemic brains using RNA sequencing. We found that BAMs express the distinct transcriptional signature than microglia and infiltrating macrophages. The enrichment of functional groups associated with the cell cycle in CD163+ cells isolated 3 days after the ischemic injury indicates the proliferative capacity of these cells. The increased number of CD163+ cells 3 days post-ischemia was corroborated by flow cytometry and detecting the increased number of CD163+ cells positive for a proliferation marker Ki67 at perivascular spaces. CD163+ cells in the ischemic brains up-regulated many inflammatory genes and parenchymal CD163+ cells expressed iNOS, which indicates acquisition of a pro-inflammatory phenotype. In mice, BAMs typically express CD206 and we found a subset of these cells expressing CD169. Chimeric mice generated by transplanting bone marrow of donor Cx3cr1gfpCCR2rfp mice to wild type hosts showed an increased number of CX3CR1+CD169+ perivascular macrophages 3 days post-ischemia. Furthermore, these cells accumulated in the brain parenchyma and we detected replacement of perivascular macrophages by peripheral monocytic cells in the sub-acute phase of stroke. In line with the animal results, post-mortem brain samples from human ischemic stroke cases showed time-dependent accumulation of CD163+ cells in the ischemic parenchyma. Our findings indicate a unique transcriptional signature of BAMs, their local proliferation and migration of inflammatory BAMs to the brain parenchyma after stroke in animal models and humans.http://www.sciencedirect.com/science/article/pii/S0969996119303973CNS border associated macrophagesRNA-sequencingIschemiaChimeric miceHuman ischemic stroke |
| spellingShingle | Wenson D. Rajan Bartosz Wojtas Bartlomiej Gielniewski Francesc Miró-Mur Jordi Pedragosa Malgorzata Zawadzka Paulina Pilanc Anna M. Planas Bozena Kaminska Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans Neurobiology of Disease CNS border associated macrophages RNA-sequencing Ischemia Chimeric mice Human ischemic stroke |
| title | Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans |
| title_full | Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans |
| title_fullStr | Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans |
| title_full_unstemmed | Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans |
| title_short | Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans |
| title_sort | defining molecular identity and fates of cns border associated macrophages after ischemic stroke in rodents and humans |
| topic | CNS border associated macrophages RNA-sequencing Ischemia Chimeric mice Human ischemic stroke |
| url | http://www.sciencedirect.com/science/article/pii/S0969996119303973 |
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