Prenatal histological, cellular, and molecular anomalies in trisomy 21 lung

Down syndrome (DS), also known as trisomy 21 (T21), is the most common human chromosomal anomaly. Although DS can affect many organ systems, lung and heart disease are the leading causes of death. An abundance of existing data suggests that lung abnormalities originate postnatally in DS. However, a...

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Bibliographic Details
Published in:The Journal of pathology 2021-09, Vol.255 (1), p.41-51
Main Authors: Danopoulos, Soula, Bhattacharya, Soumyaroop, Deutsch, Gail, Nih, Lina R, Slaunwhite, Chris, Mariani, Thomas J, Al Alam, Denise
Format: Article
Language:English
Subjects:
Cell proliferation
Coronary artery disease
Down syndrome
Down Syndrome - pathology
Down's syndrome
Extracellular matrix
Fetus
Fetuses
Gene expression
Heart diseases
histopathology
Humans
Immunohistochemistry
Interferon
Lung - abnormalities
lung development
Lung diseases
Lungs
Mesenchyme
Pathology
Phenotypes
Respiratory tract
RNAseq
Smooth muscle
Trisomy
trisomy 21
Tubules
type I interferon
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Summary:Down syndrome (DS), also known as trisomy 21 (T21), is the most common human chromosomal anomaly. Although DS can affect many organ systems, lung and heart disease are the leading causes of death. An abundance of existing data suggests that lung abnormalities originate postnatally in DS. However, a single report of branching insufficiency in DS has inferred a potential prenatal origin. The histology of T21 fetal lungs (n = 15) was assessed by an experienced pathologist. Spatial differences in cellular phenotypes were examined using immunohistochemistry (IHC). Comprehensive gene expression in prenatal T21 lungs (n = 19), and age‐matched controls (n = 19), was performed using high‐throughput RNA sequencing (RNAseq) and validated by RT‐qPCR. Histopathological abnormalities were observed in approximately half of T21 prenatal lung samples analyzed, which included dilated terminal airways/acinar tubules, dilated lymphatics, and arterial wall thickening. IHC for Ki67 revealed significant reductions in epithelial and mesenchymal cell proliferation, predominantly in tissues displaying pathology. IHC demonstrated that airway smooth muscle was reduced and discontinuous in the proximal airway in conjunction with reduced SOX2. RNAseq identified 118 genes significantly dysregulated (FDR 
ISSN:0022-3417
1096-9896
1096-9896
DOI:10.1002/path.5735