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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
1878-1551
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
055bac07-3084-41c9-806c-db12768efc1e
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
c5bcd19f-085b-44c7-8a94-448062ef0049
Gomez-Nicola, Diego
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Menassa, David A
eeb394a6-c72b-49d7-a820-95b0256c22d5
Muntslag, Tim A O
a19febb7-c244-4825-abad-a5e1d1aa80a9
Martin-Estebané, Maria
51e238f8-2ae3-4914-8e84-71f09e6b4f58
Barry-Carroll, Liam
2ea75b82-34cd-4283-9d28-8ac0f7a2bbde
Chapman, Mark A
8bac4a92-bfa7-4c3c-af29-9af852ef6383
Adorjan, Istvan
95d4918d-21fd-408d-95ed-aae325f998f1
Tyler, Teadora
e6361086-b406-4239-85f5-f5876dd8a81b
Turnbull, Bethany
055bac07-3084-41c9-806c-db12768efc1e
Rose-Zerilli, Matthew J J
29603401-e310-4054-b818-8a542c361b9a
Nicoll, James A R
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Krsnik, Zeljka
dbf71731-fb4c-45da-af8f-53513ea9bc7a
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), 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: 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
ORCID for Tim A O Muntslag: ORCID iD orcid.org/0000-0001-5624-0300
ORCID for Mark A Chapman: ORCID iD orcid.org/0000-0002-7151-723X
ORCID for James A R 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: 06 Jun 2024 01:51

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Contributors

Author: David A Menassa
Author: Tim A O Muntslag ORCID iD
Author: Maria Martin-Estebané
Author: Liam Barry-Carroll
Author: Mark A Chapman ORCID iD
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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