Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish
Summary: Microglia, the tissue-resident macrophages of the CNS, represent major targets for therapeutic intervention in a wide variety of neurological disorders. Efficient reprogramming protocols to generate microglia-like cells in vitro using patient-derived induced pluripotent stem cells will, how...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718308301 |
| _version_ | 1818570536436891648 |
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| author | Giuliano Ferrero Christopher B. Mahony Eléonore Dupuis Laurent Yvernogeau Elodie Di Ruggiero Magali Miserocchi Marianne Caron Catherine Robin David Traver Julien Y. Bertrand Valérie Wittamer |
| author_facet | Giuliano Ferrero Christopher B. Mahony Eléonore Dupuis Laurent Yvernogeau Elodie Di Ruggiero Magali Miserocchi Marianne Caron Catherine Robin David Traver Julien Y. Bertrand Valérie Wittamer |
| author_sort | Giuliano Ferrero |
| collection | DOAJ |
| description | Summary: Microglia, the tissue-resident macrophages of the CNS, represent major targets for therapeutic intervention in a wide variety of neurological disorders. Efficient reprogramming protocols to generate microglia-like cells in vitro using patient-derived induced pluripotent stem cells will, however, require a precise understanding of the cellular and molecular events that instruct microglial cell fates. This remains a challenge since the developmental origin of microglia during embryogenesis is controversial. Here, using genetic tracing in zebrafish, we uncover primitive macrophages as the unique source of embryonic microglia. We also demonstrate that this initial population is transient, with primitive microglia later replaced by definitive microglia that persist throughout adulthood. The adult wave originates from cmyb-dependent hematopoietic stem cells. Collectively, our work challenges the prevailing model establishing erythro-myeloid progenitors as the sole and direct microglial precursor and provides further support for the existence of multiple waves of microglia, which originate from distinct hematopoietic precursors. : Using zebrafish to investigate microglia ontogeny during vertebrate development, Ferrero et al. find that embryonic “primitive” microglia exclusively derive from primitive macrophages, while adult “definitive” microglia originate from cmyb-dependent hematopoietic stem cells. Keywords: developmental hematopoiesis, microglia, ontogeny, primitive macrophages, erythro-myeloid progenitors, hematopoietic stem cells, fate mapping, cmyb |
| first_indexed | 2024-12-14T13:43:03Z |
| format | Article |
| id | doaj.art-172a896c598042bea79e896a8d550db0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-14T13:43:03Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-172a896c598042bea79e896a8d550db02022-12-21T22:59:24ZengElsevierCell Reports2211-12472018-07-01241130141Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in ZebrafishGiuliano Ferrero0Christopher B. Mahony1Eléonore Dupuis2Laurent Yvernogeau3Elodie Di Ruggiero4Magali Miserocchi5Marianne Caron6Catherine Robin7David Traver8Julien Y. Bertrand9Valérie Wittamer10Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; ULB Institute of Neuroscience (UNI), ULB, Brussels, Belgium; WELBIO, ULB, Brussels, BelgiumDepartment of Pathology and Immunology, University of Geneva, School of Medicine, Geneva, SwitzerlandInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, BelgiumHubrecht Institute-KNAW and University Medical Center, Utrecht, the NetherlandsInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; ULB Institute of Neuroscience (UNI), ULB, Brussels, BelgiumInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, BelgiumInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; ULB Institute of Neuroscience (UNI), ULB, Brussels, Belgium; WELBIO, ULB, Brussels, BelgiumHubrecht Institute-KNAW and University Medical Center, Utrecht, the Netherlands; Regenerative Medicine Center, University Medical Center, Utrecht, the NetherlandsDepartment of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0380, USA; Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0380, USA; Corresponding authorDepartment of Pathology and Immunology, University of Geneva, School of Medicine, Geneva, Switzerland; Corresponding authorInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; ULB Institute of Neuroscience (UNI), ULB, Brussels, Belgium; WELBIO, ULB, Brussels, Belgium; Corresponding authorSummary: Microglia, the tissue-resident macrophages of the CNS, represent major targets for therapeutic intervention in a wide variety of neurological disorders. Efficient reprogramming protocols to generate microglia-like cells in vitro using patient-derived induced pluripotent stem cells will, however, require a precise understanding of the cellular and molecular events that instruct microglial cell fates. This remains a challenge since the developmental origin of microglia during embryogenesis is controversial. Here, using genetic tracing in zebrafish, we uncover primitive macrophages as the unique source of embryonic microglia. We also demonstrate that this initial population is transient, with primitive microglia later replaced by definitive microglia that persist throughout adulthood. The adult wave originates from cmyb-dependent hematopoietic stem cells. Collectively, our work challenges the prevailing model establishing erythro-myeloid progenitors as the sole and direct microglial precursor and provides further support for the existence of multiple waves of microglia, which originate from distinct hematopoietic precursors. : Using zebrafish to investigate microglia ontogeny during vertebrate development, Ferrero et al. find that embryonic “primitive” microglia exclusively derive from primitive macrophages, while adult “definitive” microglia originate from cmyb-dependent hematopoietic stem cells. Keywords: developmental hematopoiesis, microglia, ontogeny, primitive macrophages, erythro-myeloid progenitors, hematopoietic stem cells, fate mapping, cmybhttp://www.sciencedirect.com/science/article/pii/S2211124718308301 |
| spellingShingle | Giuliano Ferrero Christopher B. Mahony Eléonore Dupuis Laurent Yvernogeau Elodie Di Ruggiero Magali Miserocchi Marianne Caron Catherine Robin David Traver Julien Y. Bertrand Valérie Wittamer Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish Cell Reports |
| title | Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish |
| title_full | Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish |
| title_fullStr | Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish |
| title_full_unstemmed | Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish |
| title_short | Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish |
| title_sort | embryonic microglia derive from primitive macrophages and are replaced by cmyb dependent definitive microglia in zebrafish |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718308301 |
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