Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter
Abstract Multiple sclerosis (MS) is a disease of the central nervous system that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal loss. Several lines of evidence point towards a role for microglia and other brain macrophages i...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-01-01
|
| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-021-01306-3 |
| _version_ | 1819282304484245504 |
|---|---|
| author | Anneke Miedema Emma Gerrits Nieske Brouwer Qiong Jiang Laura Kracht Michel Meijer Erik Nutma Regina Peferoen-Baert Anna T. E. Pijnacker Evelyn M. Wesseling Marion H. C. Wijering Hans-Joachim Gabius Sandra Amor Bart J. L. Eggen Susanne M. Kooistra |
| author_facet | Anneke Miedema Emma Gerrits Nieske Brouwer Qiong Jiang Laura Kracht Michel Meijer Erik Nutma Regina Peferoen-Baert Anna T. E. Pijnacker Evelyn M. Wesseling Marion H. C. Wijering Hans-Joachim Gabius Sandra Amor Bart J. L. Eggen Susanne M. Kooistra |
| author_sort | Anneke Miedema |
| collection | DOAJ |
| description | Abstract Multiple sclerosis (MS) is a disease of the central nervous system that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal loss. Several lines of evidence point towards a role for microglia and other brain macrophages in disease initiation and progression, but exactly how lesion formation is triggered is currently unknown. Here, we characterized early changes in MS brain tissue through transcriptomic analysis of normal appearing white matter (NAWM). We found that NAWM was characterized by enriched expression of genes associated with inflammation and cellular stress derived from brain macrophages. Single cell RNA sequencing confirmed a stress response in brain macrophages in NAWM and identified specific microglia and macrophage subsets at different stages of demyelinating lesions. We identified both phagocytic/activated microglia and CAM clusters that were associated with various MS lesion types. These overall changes in microglia and macrophages associated with lesion development in MS brain tissue may provide therapeutic targets to limit lesion progression and demyelination. |
| first_indexed | 2024-12-24T01:13:28Z |
| format | Article |
| id | doaj.art-e6a6235939ee4b9089024f9f8ef305b6 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-24T01:13:28Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-e6a6235939ee4b9089024f9f8ef305b62022-12-21T17:22:50ZengBMCActa Neuropathologica Communications2051-59602022-01-0110111810.1186/s40478-021-01306-3Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matterAnneke Miedema0Emma Gerrits1Nieske Brouwer2Qiong Jiang3Laura Kracht4Michel Meijer5Erik Nutma6Regina Peferoen-Baert7Anna T. E. Pijnacker8Evelyn M. Wesseling9Marion H. C. Wijering10Hans-Joachim Gabius11Sandra Amor12Bart J. L. Eggen13Susanne M. Kooistra14Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Pathology, Amsterdam Neuroscience, Amsterdam UMC, VUMC SiteDepartment of Pathology, Amsterdam Neuroscience, Amsterdam UMC, VUMC SiteDepartment of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Faculty of Veterinary Medicine, Institute of Physiological Chemistry, Ludwig-Maximilians-University MunichDepartment of Pathology, Amsterdam Neuroscience, Amsterdam UMC, VUMC SiteDepartment of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen and University Medical Center Groningen (UMCG)Abstract Multiple sclerosis (MS) is a disease of the central nervous system that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal loss. Several lines of evidence point towards a role for microglia and other brain macrophages in disease initiation and progression, but exactly how lesion formation is triggered is currently unknown. Here, we characterized early changes in MS brain tissue through transcriptomic analysis of normal appearing white matter (NAWM). We found that NAWM was characterized by enriched expression of genes associated with inflammation and cellular stress derived from brain macrophages. Single cell RNA sequencing confirmed a stress response in brain macrophages in NAWM and identified specific microglia and macrophage subsets at different stages of demyelinating lesions. We identified both phagocytic/activated microglia and CAM clusters that were associated with various MS lesion types. These overall changes in microglia and macrophages associated with lesion development in MS brain tissue may provide therapeutic targets to limit lesion progression and demyelination.https://doi.org/10.1186/s40478-021-01306-3Multiple sclerosisBrain macrophagesMicrogliaSingle-cell RNAseqNormal appearing white matter |
| spellingShingle | Anneke Miedema Emma Gerrits Nieske Brouwer Qiong Jiang Laura Kracht Michel Meijer Erik Nutma Regina Peferoen-Baert Anna T. E. Pijnacker Evelyn M. Wesseling Marion H. C. Wijering Hans-Joachim Gabius Sandra Amor Bart J. L. Eggen Susanne M. Kooistra Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter Acta Neuropathologica Communications Multiple sclerosis Brain macrophages Microglia Single-cell RNAseq Normal appearing white matter |
| title | Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter |
| title_full | Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter |
| title_fullStr | Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter |
| title_full_unstemmed | Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter |
| title_short | Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter |
| title_sort | brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter |
| topic | Multiple sclerosis Brain macrophages Microglia Single-cell RNAseq Normal appearing white matter |
| url | https://doi.org/10.1186/s40478-021-01306-3 |
| work_keys_str_mv | AT annekemiedema brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT emmagerrits brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT nieskebrouwer brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT qiongjiang brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT laurakracht brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT michelmeijer brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT eriknutma brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT reginapeferoenbaert brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT annatepijnacker brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT evelynmwesseling brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT marionhcwijering brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT hansjoachimgabius brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT sandraamor brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT bartjleggen brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter AT susannemkooistra brainmacrophagesacquiredistincttranscriptomesinmultiplesclerosislesionsandnormalappearingwhitematter |