RT info:eu-repo/semantics/article
T1 Genetic and Morphological Features of Human iPSC-Derived Neurons with Chromosome 15q11.2 (BP1-BP2) Deletions
A1 Das, Dhanjit K.
A1 Tapias, Victor
A1 D''Aiuto, Leonardo
A1 Chowdari, Kodavali V.
A1 Francis, Lily
A1 Zhi, Yun
A1 Ghosh, Ayantika
A1 Surti, Urvashi
A1 Tischfield, Jay
A1 Sheldon, Michael
A1 Moore, Jennifer C.
A1 Fish, Ken
A1 Nimgaonkar, Vishwajit L.
AB Background: Copy number variation on chromosome 15q11.2 (BP1-BP2) causes deletion of CYFIP1, NIPA1, NIPA2 and TUBGCP5; it also affects brain structure and elevates risk for several neurodevelopmental disorders that are associated with dendritic spine abnormalities. In rodents, altered cyfip1 expression changes dendritic spine morphology, motivating analyses of human neuronal cells derived from iPSCs (iPSC-neurons).Methods: iPSCs were generated from a mother and her offspring, both carrying the 15q11.2 (BP1-BP2) deletion, and a non-deletion control. Gene expression in the deletion region was estimated using quantitative real-time PCR assays. Neural progenitor cells (NPCs) and iPSC-neurons were characterized using immunocytochemistry.Results: CYFIP1, NIPA1, NIPA2 and TUBGCP5 gene expression was lower in iPSCs, NPCs and iPSC-neurons from the mother and her offspring in relation to control cells. CYFIP1 and PSD95 protein levels were lower in iPSC-neurons derived from the CNV bearing individuals using Western blot analysis. At 10 weeks post-differentiation, iPSC-neurons appeared to show dendritic spines and qualitative analysis suggested that dendritic morphology was altered in 15q11.2 deletion subjects compared with control cells.Conclusions: The 15q11.2 (BP1-BP2) deletion is associated with reduced expression of four genes in iPSC-derived neuronal cells; it may also be associated altered iPSC-neuron dendritic morphology.
SN 2673-3005
YR 2015
FD 2015
LK https://uvadoc.uva.es/handle/10324/63885
UL https://uvadoc.uva.es/handle/10324/63885
LA eng
NO Molecular Neuropsychiatry, Julio 2015, vol. 1, n. 2. p. 116-123
NO Producción Científica
DS UVaDOC
RD 01-jun-2024