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E-GEOD-63057 - 7q11.23 dosage-dependent dysregulation in the human pluripotent state primes aberrant transcriptional programs in disease-relevant lineages (ChIP-Seq)

Released on 15 December 2014, last updated on 2 January 2015
Homo sapiens
Samples (22)
Protocols (1)
We apply the cellular reprogramming experimental paradigm to two disorders caused by symmetrical copy number variations (CNV) of 7q11.23 and displaying a striking combination of shared as well as symmetrically opposite phenotypes: Williams Beuren syndrome (WBS) and 7q microduplication syndrome (7dupASD). Through a uniquely large and informative cohort of transgene-free patient-derived induced pluripotent stem cells (iPSC), along with their differentiated derivatives, we find that 7q11.23 CNV disrupt transcriptional circuits in disease-relevant pathways already at the pluripotent state. These alterations are then selectively amplified upon differentiation into disease-relevant lineages, thereby establishing the value of large iPSC cohorts in the elucidation of disease-relevant developmental pathways. In addition, we functionally define the quota of transcriptional dysregulation specifically caused by dosage imbalances in GTF2I (also known as TFII-I), a transcription factor in 7q11.23 thought to play a critical role in the two conditions, which we found associated to key repressive chromatin modifiers. Finally, we created an open-access web-based platform (accessible at ) to make accessible our multi-layered datasets and integrate contributions by the entire community working on the molecular dissection of the 7q11.23 syndromes. We tested three antibodies against GTF2I for ChIP-seq application, and selected the one showing the best enrichment to profile GTF2I bindings across a panel of 12 iPSC lines established from patients harbouring a 7q11.23 hemi-deletion (WBS; 5 patients) or microduplication (7dupASD; 2 patients), as well as from two independent controls individuals.
Experiment type
Giuseppe Testa <>, Angelo Selicorni, Antonio Adamo, Bartolomeo Augello, Brad Hamilton, Carmela Fusco, Christian Unger, Elisa Biamino, Emilio Donti, Giancarlo Pruneri, Giuseppe D'Agostino, Giuseppe Merla, Josh Chenoweth, Lucia Micale, Massimo Carella, Matteo Zanella, Orazio Palumbo, Paolo Prontera, Pierre-Luc Germain, Ronald McKay, Sina Atashpaz, Veronica Albertin
Exp. designProtocolsVariablesProcessedSeq. reads