Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing.

Humans Child Adolescent Transcriptome Microglia / metabolism Longevity Phagocytosis Sequence Analysis, RNA
Ex vivo human microglia Gene regulatory network Transcriptional heterogeneity scRNA-seq

Journal

Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974

Informations de publication

Date de publication:
30 May 2023
Historique:
received: 29 05 2022
accepted: 17 05 2023
medline: 1 6 2023
pubmed: 31 5 2023
entrez: 30 5 2023
Statut: epublish

Résumé

Microglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis. In this study, we aimed to characterize the transcriptional landscape of ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, and adult brain samples. We further confirmed our transcriptional observations using ELISA and RNAscope. We showed that pre-natal microglia have a distinct transcriptional and regulatory signature relative to their post-natal counterparts that includes an upregulation of phagocytic pathways. We confirmed upregulation of CD36, a positive regulator of phagocytosis, in pre-natal samples compared to adult samples in situ. Moreover, we showed adult microglia have more pro-inflammatory signature compared to microglia from other developmental ages. We indicated that adult microglia are more immune responsive by secreting increased levels of pro-inflammatory cytokines in response to LPS treatment compared to the pre-natal microglia. We further validated in situ up-regulation of IL18 and CXCR4 in human adult brain section compared to the pre-natal brain section. Finally, trajectory analysis indicated that the transcriptional signatures adopted by microglia throughout development are in response to a changing brain microenvironment and do not reflect predetermined developmental states. In all, this study provides unique insight into the development of human microglia and a useful reference for understanding microglial contribution to developmental and age-related human disease.

Sections du résumé

BACKGROUND BACKGROUND
Microglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis.
METHOD METHODS
In this study, we aimed to characterize the transcriptional landscape of ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, and adult brain samples. We further confirmed our transcriptional observations using ELISA and RNAscope.
RESULTS RESULTS
We showed that pre-natal microglia have a distinct transcriptional and regulatory signature relative to their post-natal counterparts that includes an upregulation of phagocytic pathways. We confirmed upregulation of CD36, a positive regulator of phagocytosis, in pre-natal samples compared to adult samples in situ. Moreover, we showed adult microglia have more pro-inflammatory signature compared to microglia from other developmental ages. We indicated that adult microglia are more immune responsive by secreting increased levels of pro-inflammatory cytokines in response to LPS treatment compared to the pre-natal microglia. We further validated in situ up-regulation of IL18 and CXCR4 in human adult brain section compared to the pre-natal brain section. Finally, trajectory analysis indicated that the transcriptional signatures adopted by microglia throughout development are in response to a changing brain microenvironment and do not reflect predetermined developmental states.
CONCLUSION CONCLUSIONS
In all, this study provides unique insight into the development of human microglia and a useful reference for understanding microglial contribution to developmental and age-related human disease.

Identifiants

DOI: 10.1186/s12974-023-02809-7 PMID: 37254100 PMC: PMC10230780
pubmed: 37254100
doi: 10.1186/s12974-023-02809-7
pii: 10.1186/s12974-023-02809-7
pmc: PMC10230780
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

132

Informations de copyright

© 2023. The Author(s).

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Auteurs

Moein Yaqubi (M)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Adam M R Groh (AMR)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Marie-France Dorion (MF)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Elia Afanasiev (E)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Julia Xiao Xuan Luo (JXX)

Department of Microbiology and Immunology, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Hadi Hashemi (H)

Department of Electrical and Electronic Engineering, Shiraz University of Technology, Shiraz, Fars, Iran.

Sarthak Sinha (S)

Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada.

Nicholas W Kieran (NW)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Manon Blain (M)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Qiao-Ling Cui (QL)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Jeff Biernaskie (J)

Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada.

Myriam Srour (M)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
Department of Pediatric Neurosurgery, Montreal Children's Hospital, Montreal, QC, Canada.

Roy Dudley (R)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
Department of Pediatric Neurosurgery, Montreal Children's Hospital, Montreal, QC, Canada.

Jeffery A Hall (JA)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Joshua A Sonnen (JA)

Departments of Pathology, Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

Nathalie Arbour (N)

Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de L, Université de Montréal (CRCHUM), Montreal, QC, Canada.
Department of Neurosciences, Université de Montréal, Montreal, QC, Canada.

Alexandre Prat (A)

Department of Neurosciences, Université de Montréal, Montreal, QC, Canada.

Jo Anne Stratton (JA)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Jack Antel (J)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Luke M Healy (LM)

Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada. luke.healy@mcgill.ca.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Analysis of the microglia transcriptome across...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Analysis of the microglia transcriptome across...
questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Analysis of the microglia transcriptome across...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Analysis of the microglia transcriptome across...
questionsmedicales.fr › Cellules › Névroglie › Microglie › Analysis of the microglia transcriptome across...
questionsmedicales.fr › Phénomènes physiologiques › Longévité › Analysis of the microglia transcriptome across...
questionsmedicales.fr › Phénomènes du système immunitaire › Phagocytose › Analysis of the microglia transcriptome across...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Analysis of the microglia transcriptome across...