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The spatiotemporal dynamics of microglia across the human lifespan

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
1534-5807
2127-2139.e6
Menassa, David
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Muntslag, Tim Arno Othni
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Martin estebane, Maria
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Barry-Carroll, Liam Anthony
2ea75b82-34cd-4283-9d28-8ac0f7a2bbde
Chapman, Mark
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Adorjan, Istvan
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Turnbull, Bethany
055bac07-3084-41c9-806c-db12768efc1e
Rose-Zerilli, Matthew
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Nicoll, James
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Krsnik, Zeljka
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Kostovic, Ivica
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Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Menassa, David
eeb394a6-c72b-49d7-a820-95b0256c22d5
Muntslag, Tim Arno Othni
a19febb7-c244-4825-abad-a5e1d1aa80a9
Martin estebane, Maria
51e238f8-2ae3-4914-8e84-71f09e6b4f58
Barry-Carroll, Liam Anthony
2ea75b82-34cd-4283-9d28-8ac0f7a2bbde
Chapman, Mark
8bac4a92-bfa7-4c3c-af29-9af852ef6383
Adorjan, Istvan
95d4918d-21fd-408d-95ed-aae325f998f1
Turnbull, Bethany
055bac07-3084-41c9-806c-db12768efc1e
Rose-Zerilli, Matthew
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Krsnik, Zeljka
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Kostovic, Ivica
22ae314c-b5bc-4a14-a385-b3310542a2b1
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5

Menassa, David, Muntslag, Tim Arno Othni, Martin estebane, Maria, Barry-Carroll, Liam Anthony, Chapman, Mark, Adorjan, Istvan, Turnbull, Bethany, Rose-Zerilli, Matthew, Nicoll, James, Krsnik, Zeljka, Kostovic, Ivica and Gomez-Nicola, Diego (2022) The spatiotemporal dynamics of microglia across the human lifespan. Developmental Cell, 57 (17), 2127-2139.e6. (doi:10.1016/j.devcel.2022.07.015).

Record type: Article

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) - Accepted Manuscript
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More information

Accepted/In Press date: 26 July 2022
Published date: 16 August 2022
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: 1534-5807
PURE UUID: 18ee45bd-abf4-42dc-993c-28aa5296dffa
ORCID for Mark Chapman: ORCID iD orcid.org/0000-0002-7151-723X
ORCID for Matthew Rose-Zerilli: ORCID iD orcid.org/0000-0002-1064-5350
ORCID for James Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 30 Aug 2022 16:43
Last modified: 23 Feb 2023 03:00

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Contributors

Author: David Menassa
Author: Tim Arno Othni Muntslag
Author: Maria Martin estebane
Author: Liam Anthony Barry-Carroll
Author: Mark Chapman ORCID iD
Author: Istvan Adorjan
Author: Bethany Turnbull
Author: James Nicoll ORCID iD
Author: Zeljka Krsnik
Author: Ivica Kostovic

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