Cited by 129Williams Syndrome ResearchPluripotent Stem Cells ResearchGenomic variations and chromosomal abnormalities

7q11.23 dosage-dependent dysregulation in human pluripotent stem cells affects transcriptional programs in disease-relevant lineages

Adamo, Antonio, Atashpaz, Sina, Germain, Pierre-Luc, Zanella, Matteo, D'Agostino, Giuseppe, Albertin, Veronica, Chenoweth, Josh, Micale, Lucia +14 more·2015·Nature Genetics

Abstract

Cell reprogramming promises to make characterization of the impact of human genetic variation on health and disease experimentally tractable by enabling the bridging of genotypes to phenotypes in developmentally relevant human cell lineages. Here we apply this paradigm to two disorders caused by symmetrical copy number variations of 7q11.23, which display a striking combination of shared and symmetrically opposite phenotypes--Williams-Beuren syndrome and 7q-microduplication syndrome. Through analysis of transgene-free patient-derived induced pluripotent stem cells and their differentiated derivatives, we find that 7q11.23 dosage imbalance disrupts transcriptional circuits in disease-relevant pathways beginning in the pluripotent state. These alterations are then selectively amplified upon differentiation of the pluripotent cells into disease-relevant lineages. A considerable proportion of this transcriptional dysregulation is specifically caused by dosage imbalances in GTF2I, which encodes a key transcription factor at 7q11.23 that is associated with the LSD1 repressive chromatin complex and silences its dosage-sensitive targets.

Integrity signals

Registry

Crossref · 10.1038/ng.3169

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Adamo, A., Atashpaz, S., Germain, P.-L., Zanella, M., D'Agostino, G., Albertin, V., Chenoweth, J., Micale, L., Fusco, C., Unger, C., Augello, B., Palumbo, O., Hamilton, B., Carella, M., Donti, E., Pruneri, G., Selicorni, A., Biamino, E., Prontera, P., McKay, R., Merla, G., & Testa, G.
Affiliations
  • European Institute of Oncology (IT)
  • Lieber Institute for Brain Development (US)
  • Casa Sollievo della Sofferenza (IT)
  • University of Sheffield (GB)
  • University of Perugia (IT)
  • Azienda Ospedaliera San Gerardo (IT)
  • University of Turin (IT)
  • University of Milan (IT)
Corresponding author
Testa, Giuseppe
Venue
Nature Genetics
Published
2014-12-15
Volume
47
Issue
2
Pages
132-141
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2032600544
Cited by
129
References
70
Citations by year
2026: 6 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 19 · 2019: 11 · 2018: 13 · 2017: 14 · 2016: 16 · 2015: 11
FWCI
4.71
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
copy number variation, dosage imbalance, induced pluripotent stem cells, GTF2I, Williams syndrome, transcriptional dysregulation, LSD1, chromatin silencing, neurocognitive phenotype, patient-derived cell models, cell differentiation
MeSH terms
Cell Differentiation, Chromosomes, Human, Pair 7, Gene Expression Regulation, Humans, Phenotype, Cohort Studies, Sequence Analysis, RNA, Gene Dosage, Williams Syndrome, Cell Lineage, Transcription Factors, TFII, Oligonucleotide Array Sequence Analysis, Gene Duplication, Gene Expression Profiling, Pluripotent Stem Cells, Comparative Genomic Hybridization, Histone Demethylases, DNA Copy Number Variations

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review