Multiomics Analysis of a
DNAH5
airway organoid
immune response
multiomics analysis
primary ciliary dyskinesia
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
12 12 2022
12 12 2022
Historique:
received:
13
11
2022
revised:
08
12
2022
accepted:
10
12
2022
entrez:
23
12
2022
pubmed:
24
12
2022
medline:
27
12
2022
Statut:
epublish
Résumé
Dynein axonemal heavy chain 5 (DNAH5) is the most mutated gene in primary ciliary dyskinesia (PCD), leading to abnormal cilia ultrastructure and function. Few studies have revealed the genetic characteristics and pathogenetic mechanisms of PCD caused by DNAH5 mutation. Here, we established a child PCD airway organoid directly from the bronchoscopic biopsy of a patient with the DNAH5 mutation. The motile cilia in the organoid were observed and could be stably maintained for an extended time. We further found abnormal ciliary function and a decreased immune response caused by the DNAH5 mutation through single-cell RNA sequencing (scRNA-Seq) and proteomic analyses. Additionally, the directed induction of the ciliated cells, regulated by TGF-β/BMP and the Notch pathway, also increased the expression of inflammatory cytokines. Taken together, these results demonstrated that the combination of multiomics analysis and organoid modelling could reveal the close connection between the immune response and the DNAH5 gene.
Identifiants
pubmed: 36552777
pii: cells11244013
doi: 10.3390/cells11244013
pmc: PMC9776854
pii:
doi:
Substances chimiques
Axonemal Dyneins
EC 3.6.4.2
Transforming Growth Factor beta
0
DNAH5 protein, human
EC 3.6.4.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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