The spatiotemporal dynamics of microglia across the human lifespan
The spatiotemporal dynamics of microglia across the human lifespan
Microglia, the brain's resident macrophages, shape neural development and are key neuroimmune hubs in the pathological signatures of neurodevelopmental disorders. Despite the importance of microglia, their development has not been carefully examined in the human brain, and most of our knowledge derives from rodents. We aimed to address this gap in knowledge by establishing an extensive collection of 97 post-mortem tissues in order to enable quantitative, sex-matched, detailed analysis of microglia across the human lifespan. We identify the dynamics of these cells in the human telencephalon, describing waves in microglial density across gestation, infancy, and childhood, controlled by a balance of proliferation and apoptosis, which track key neurodevelopmental milestones. These profound changes in microglia are also observed in bulk RNA-seq and single-cell RNA-seq datasets. This study provides a detailed insight into the spatiotemporal dynamics of microglia across the human lifespan and serves as a foundation for elucidating how microglia contribute to shaping neurodevelopment in humans.
RNA-seq, apoptosis, neurodevelopment, proliferation, single-cell RNA-seq
2127-2139.e6
Menassa, David A
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Muntslag, Tim A O
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Martin-Estebané, Maria
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Barry-Carroll, Liam
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Chapman, Mark A
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Adorjan, Istvan
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Tyler, Teadora
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Turnbull, Bethany
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Rose-Zerilli, Matthew J J
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Nicoll, James A R
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Krsnik, Zeljka
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Kostovic, Ivica
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Gomez-Nicola, Diego
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12 September 2022
Menassa, David A
eeb394a6-c72b-49d7-a820-95b0256c22d5
Muntslag, Tim A O
a19febb7-c244-4825-abad-a5e1d1aa80a9
Martin-Estebané, Maria
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Barry-Carroll, Liam
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Chapman, Mark A
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Adorjan, Istvan
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Tyler, Teadora
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Turnbull, Bethany
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Rose-Zerilli, Matthew J J
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Nicoll, James A R
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Krsnik, Zeljka
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Kostovic, Ivica
c5bcd19f-085b-44c7-8a94-448062ef0049
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Menassa, David A, Muntslag, Tim A O, Martin-Estebané, Maria, Barry-Carroll, Liam, Chapman, Mark A, Adorjan, Istvan, Tyler, Teadora, Turnbull, Bethany, Rose-Zerilli, Matthew J J, Nicoll, James A R, Krsnik, Zeljka, Kostovic, Ivica and Gomez-Nicola, Diego
(2022)
The spatiotemporal dynamics of microglia across the human lifespan.
Developmental Cell, 57 (17), .
(doi:10.1016/j.devcel.2022.07.015).
Abstract
Microglia, the brain's resident macrophages, shape neural development and are key neuroimmune hubs in the pathological signatures of neurodevelopmental disorders. Despite the importance of microglia, their development has not been carefully examined in the human brain, and most of our knowledge derives from rodents. We aimed to address this gap in knowledge by establishing an extensive collection of 97 post-mortem tissues in order to enable quantitative, sex-matched, detailed analysis of microglia across the human lifespan. We identify the dynamics of these cells in the human telencephalon, describing waves in microglial density across gestation, infancy, and childhood, controlled by a balance of proliferation and apoptosis, which track key neurodevelopmental milestones. These profound changes in microglia are also observed in bulk RNA-seq and single-cell RNA-seq datasets. This study provides a detailed insight into the spatiotemporal dynamics of microglia across the human lifespan and serves as a foundation for elucidating how microglia contribute to shaping neurodevelopment in humans.
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Menassa et al 2022 (accepted version)
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Accepted/In Press date: 26 July 2022
Published date: 12 September 2022
Additional Information:
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Keywords:
RNA-seq, apoptosis, neurodevelopment, proliferation, single-cell RNA-seq
Identifiers
Local EPrints ID: 468853
URI: http://eprints.soton.ac.uk/id/eprint/468853
ISSN: 1878-1551
PURE UUID: 18ee45bd-abf4-42dc-993c-28aa5296dffa
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Date deposited: 30 Aug 2022 16:43
Last modified: 17 Mar 2024 03:31
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Contributors
Author:
David A Menassa
Author:
Tim A O Muntslag
Author:
Maria Martin-Estebané
Author:
Liam Barry-Carroll
Author:
Istvan Adorjan
Author:
Teadora Tyler
Author:
Bethany Turnbull
Author:
Matthew J J Rose-Zerilli
Author:
Zeljka Krsnik
Author:
Ivica Kostovic
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