Modeling Human Cytomegalovirus-Induced Microcephaly in Human iPSC-Derived Brain Organoids.
Induced pluripotent stem cells
brain organoids
calcium signaling
human cytomegalovirus
iPSCs
microcephaly
neural network
neural progenitor cells
neutralizing antibody
pentamer complex
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
21 04 2020
21 04 2020
Historique:
received:
02
05
2019
revised:
16
01
2020
accepted:
28
02
2020
entrez:
18
11
2020
pubmed:
19
11
2020
medline:
19
11
2020
Statut:
epublish
Résumé
Although congenital infection by human cytomegalovirus (HCMV) is well recognized as a leading cause of neurodevelopmental defects, HCMV neuropathogenesis remains poorly understood. A major challenge for investigating HCMV-induced abnormal brain development is the strict CMV species specificity, which prevents the use of animal models to directly study brain defects caused by HCMV. We show that infection of human-induced pluripotent-stem-cell-derived brain organoids by a "clinical-like" HCMV strain results in reduced brain organoid growth, impaired formation of cortical layers, and abnormal calcium signaling and neural network activity. Moreover, we show that the impeded brain organoid development caused by HCMV can be prevented by neutralizing antibodies (NAbs) that recognize the HCMV pentamer complex. These results demonstrate in a three-dimensional cellular biosystem that HCMV can impair the development and function of the human brain and provide insights into the potential capacity of NAbs to mitigate brain defects resulted from HCMV infection.
Identifiants
pubmed: 33205055
doi: 10.1016/j.xcrm.2020.100002
pii: S2666-3791(20)30002-1
pmc: PMC7659592
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
100002Subventions
Organisme : NINDS NIH HHS
ID : R35 NS097370
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI128913
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA181045
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA077544
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS047344
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG061794
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD079918
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056305
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA111412
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA107399
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG061171
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI103960
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI131130
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
F.W., F.C., and D.J.D. receive royalty payments from Helocyte Inc. D.J.D. chairs the Scientific Advisory Board of Helocyte Inc., and he has an equity interest in Helocyte Inc. F.W., F.C., and D.J.D. hold patents US10487139B2 and US10376575B2.
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