Dataset Information

Single-cell Landscape Analysis Reveals HSA21 Induced Regulatory Network in Mammalian Down Syndrome

ABSTRACT: Down syndrome (DS), characterized by various malfunctions, is the most common genetic chromosomal disorder. As DS population size keeps growing and most of them live beyond their puberty, their early‐onset health problems come into view. However, the molecular alterations have not been thoroughly surveyed before. Here we provide the first description of DS in single-cell resolution, including human and mouse, covering seven different organs. With 71934 mouse cells and 93207 human cells employed, we systematically revealed DS cells, across different cell types and different organs suffering from serious cellular stresses. We observed senescence stresses including ribosomal protein gene accumulation, mitochondrial dysfunction, apoptosis, and sterile inflammation in fetus DS cells. We further raised an HSA21 gene-induced regulatory network driving genome-wide expression alteration. Hence, this study provides valuable information to understand the pathological processes under DS condition.

ORGANISM(S): Homo sapiens

PROVIDER: GSE155409 | GEO | 2023/12/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and associated with an array of deleterious phenotypes, including mental retardation, heart defects and immunodeficiency. Spatio-temporal patterns of genome-wide expression are critical to the understanding of DS. We used a Human Exon microarray to characterize gene expression in peripheral blood cells derived from DS and control individuals from two age groups: neonate (N) and child (C). A total of 174 transcript clusters (gene-level) with eight located on Hsa21 in N group and 383 transcript clusters including 57 on Hsa21 in C group were significantly dysregulated in DS individuals. Except for 22 commonly dysregulated genes in the two groups, the remaining dysregulated genes were different between N and C groups, reflecting temporally dynamic variation in gene expression in DS. Dramatically fewer dysregulated Hsa21 genes in N group than those in C group suggested that triplication of Hsa21 per se induces a moderate deregulation at early developmental stages. Further functional analysis revealed that the dysregulated genes in DS were significantly enriched in two KEGG pathways in N group and six pathways in C group. These pathways included leukocyte trans-endothelial migration, B cell receptor signaling pathway and primary immunodeficiency, etc., which causally implicated dysfunctional immunity in DS. Our results provided a comprehensive picture of expression patterns of DS at the two developmental stages and point towards candidate genes and molecular pathways potentially associated with the immune dysfunction in DS. All 37 samples, including 15 DS patients and 22 control individuals were analysized and divided into two age-matched groups: N group (5 DS versus 7 control individuals, age: 3 days to 38 days) and C group (10 DS versus 15 control individuals, age: 1 year to 13 years). N group includes DS (D11-D15) and Control (C16-C22), and C group includes DS (D1-D10) and Control (C1-C15).

Dataset Information

Single-cell Landscape Analysis Reveals HSA21 Induced Regulatory Network in Mammalian Down Syndrome

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets