Erosion of human X chromosome inactivation causes major remodeling of the iPSC proteome

• DOI: 10.1016/j.celrep.2021.109032
• Publication Date: 2021-04-27T16:21:01Z
• Authors: Alejandro J. Brenes; Harunori Yoshikawa; Dalila Bensaddek; Bogdan Mirauta; Daniel Seaton; Jens L. Hukelmann; Hao Jiang; Oliver Stegle; Angus I. Lamond
• Keywords: XIST; Dosage compensation; ribosome biogenesis; Proteome; Ribosomal protein

X chromosome inactivation (XCI) is a dosage compensation mechanism in female mammals whereby transcription from one repressed. Analysis of human induced pluripotent stem cells (iPSCs) derived donors identified that low levels XIST RNA correlated strongly with erosion XCI. Proteomic analysis, sequencing (RNA-seq), and polysome profiling showed XCI resulted amplified protein expression X-linked genes, providing proteomic characterization skewed compensation. Increased was also detected autosomal genes without an mRNA increase, thus altering the protein-RNA correlation between autosomes. XCI-eroded lines display ∼13% increase total cell content, increased ribosomal proteins, ribosome biogenesis translation factors, levels. We conclude iPSCs causes remodeling proteome, affecting much wider range proteins disease-linked loci than previously realized.