An in vivo neuroimmune organoid model to study human microglia phenotypes.
Human microglia
autism spectrum disorders
brain organoids
iPSCs
microglia in vivo identity
microglia surveillance
neuro-immune interactions
organoid transplantation
xenotransplantation
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
11 05 2023
11 05 2023
Historique:
received:
03
03
2022
revised:
18
12
2022
accepted:
14
04
2023
pmc-release:
11
05
2024
medline:
15
5
2023
pubmed:
13
5
2023
entrez:
12
5
2023
Statut:
ppublish
Résumé
Microglia are specialized brain-resident macrophages that play crucial roles in brain development, homeostasis, and disease. However, until now, the ability to model interactions between the human brain environment and microglia has been severely limited. To overcome these limitations, we developed an in vivo xenotransplantation approach that allows us to study functionally mature human microglia (hMGs) that operate within a physiologically relevant, vascularized immunocompetent human brain organoid (iHBO) model. Our data show that organoid-resident hMGs gain human-specific transcriptomic signatures that closely resemble their in vivo counterparts. In vivo two-photon imaging reveals that hMGs actively engage in surveilling the human brain environment, react to local injuries, and respond to systemic inflammatory cues. Finally, we demonstrate that the transplanted iHBOs developed here offer the unprecedented opportunity to study functional human microglia phenotypes in health and disease and provide experimental evidence for a brain-environment-induced immune response in a patient-specific model of autism with macrocephaly.
Identifiants
pubmed: 37172564
pii: S0092-8674(23)00418-X
doi: 10.1016/j.cell.2023.04.022
pmc: PMC10284271
mid: NIHMS1894854
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2111-2126.e20Subventions
Organisme : NIA NIH HHS
ID : R01 AG056306
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056511
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG057706
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS108034
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG061060
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG056306
Pays : United States
Organisme : NINDS NIH HHS
ID : U19 NS123719
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014195
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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