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DOI	10.1073/pnas.2014723118
	Consequences of aneuploidy in human fibroblasts with trisomy 21
	Hwang S.; Cavaliere P.; Li R.; Zhu L.J.; Dephoure N.; Torres E.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	An extra copy of chromosome 21 causes Down syndrome, the most common genetic disease in humans. The mechanisms contributing to aneuploidy-related pathologies in this syndrome, independent of the identity of the triplicated genes, are not well defined. To characterize aneuploidy-driven phenotypes in trisomy 21 cells, we performed global transcriptome, proteome, and phenotypic analyses of primary human fibroblasts from individuals with Patau (trisomy 13), Edwards (trisomy 18), or Down syndromes. On average, mRNA and protein levels were increased by 1.5-fold in all trisomies, with a subset of proteins enriched for subunits of macromolecular complexes showing signs of posttranscriptional regulation. These results support the lack of evidence for widespread dosage compensation or dysregulation of chromosomal domains in human autosomes. Furthermore, we show that several aneuploidy-associated phenotypes are present in trisomy 21 cells, including lower viability and increased dependency on serine-driven lipid synthesis. Our studies establish a critical role of aneuploidy, independent of triplicated gene identity, in driving cellular defects associated with trisomy 21. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Aneuploidy; Dosage compensation; Down syndrome; Sphingolipids; Trisomy 21
语种	英语
scopus关键词	collagen type 18; lipid; messenger RNA; mitochondrial DNA; serine; telomerase reverse transcriptase; transcription factor GATA 6; aneuploidy; Article; autosome; cell viability; Down syndrome; Edwards syndrome; fibroblast; gene dosage; human; lipogenesis; macromolecule; phenotype; priority journal; protein expression; protein processing; proteomics; transcriptomics; trisomy 13; trisomy 21
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180708
作者单位	Department of Molecular, Cell and Cancer Biology, University of Massachusetts, Medical School, Worcester, MA 01605, United States; Department of Biochemistry, Weill Cornell Medical College, New York, NY 10021, United States; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States; Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, United States
推荐引用方式 GB/T 7714	Hwang S.,Cavaliere P.,Li R.,et al. Consequences of aneuploidy in human fibroblasts with trisomy 21[J],2021,118(6).
APA	Hwang S.,Cavaliere P.,Li R.,Zhu L.J.,Dephoure N.,&Torres E.M..(2021).Consequences of aneuploidy in human fibroblasts with trisomy 21.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Hwang S.,et al."Consequences of aneuploidy in human fibroblasts with trisomy 21".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).