7q11.23 dosage-dependent dysregulation in the human pluripotent state primes aberrant transcriptional programs in disease-relevant lineages (RNAseq)

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Giuseppe Testa 

PROVIDER: E-GEOD-63055 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress