Down Syndrome Altered Cell Composition in Blood, Brain, and Buccal Swab Samples Profiled by DNA-Methylation-Based Cell-Type Deconvolution.
DNA methylation
brain deconvolution
cell deconvolution
down syndrome
epigenetics
immune cell deconvolution
trisomy 21
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
15 04 2023
15 04 2023
Historique:
received:
27
03
2023
revised:
10
04
2023
accepted:
11
04
2023
medline:
17
5
2023
pubmed:
16
5
2023
entrez:
16
5
2023
Statut:
epublish
Résumé
Down syndrome (DS) is a genetic disorder caused by an extra copy of chromosome 21 that presents developmental dysfunction and intellectual disability. To better understand the cellular changes associated with DS, we investigated the cell composition in blood, brain, and buccal swab samples from DS patients and controls using DNA methylation-based cell-type deconvolution. We used genome-scale DNA methylation data from Illumina HumanMethylation450k and HumanMethylationEPIC arrays to profile cell composition and trace fetal lineage cells in blood samples (DS N = 46; control N = 1469), brain samples from various regions (DS N = 71; control N = 101), and buccal swab samples (DS N = 10; control N = 10). In early development, the number of cells from the fetal lineage in the blood is drastically lower in DS patients (Δ = 17.5%), indicating an epigenetically dysregulated maturation process for DS patients. Across sample types, we observed significant alterations in relative cell-type proportions for DS subjects compared with the controls. Cell-type proportion alterations were present in samples from early development and adulthood. Our findings provide insight into DS cellular biology and suggest potential cellular interventional targets for DS.
Identifiants
pubmed: 37190077
pii: cells12081168
doi: 10.3390/cells12081168
pmc: PMC10136493
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : P20GM104416/8299
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023108
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216265
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA253976
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA216265
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA253976
Pays : United States
Organisme : NCI NIH HHS
ID : P30CA023108
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM104416
Pays : United States
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