title: Genetic and morphological features of human iPSC-derived neurons with chromosome 15q11.2 (BP1-BP2) deletions.
abstract: BACKGROUND
  Copy number variation on chromosome 15q11.2 (BP1-BP2) causes deletion ofCYFIP1, NIPA1, NIPA2andTUBGCP5; it also affects brain structure and elevates risk for several neurodevelopmental disorders that are associated with dendritic spine abnormalities. In rodents, alteredcyfip1expression 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, NIPA2andTUBGCP5gene 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.
authors.affiliation: University of Pittsburgh School of Medicine, Dept of Psychiatry.
authors.forename: D K
authors.initials: DK
authors.lastname: Das
authors.affiliation: University of Pittsburgh, Dept. of Neurology.
authors.forename: V
authors.initials: V
authors.lastname: Tapias
authors.affiliation: University of Pittsburgh School of Medicine, Dept of Psychiatry.
authors.forename: L
authors.initials: L
authors.lastname: D'Aiuto
authors.affiliation: University of Pittsburgh School of Medicine, Dept of Psychiatry.
authors.forename: K V
authors.initials: KV
authors.lastname: Chowdari
authors.affiliation: University of Pittsburgh School of Medicine, Dept of Psychiatry.
authors.forename: L
authors.initials: L
authors.lastname: Francis
authors.affiliation: University of Pittsburgh School of Medicine, Dept of Psychiatry ; Tsinghua University School of Medicine.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhi
authors.affiliation: University of Pittsburgh School of Medicine, Dept of Psychiatry.
authors.forename: Bhattacharjee A
authors.initials: BA
authors.lastname: Ghosh
authors.affiliation: University of Pittsburgh School of Medicine, Dept. of Pathology ; University of Pittsburgh, Graduate School of Public Health, Department of Human Genetics.
authors.forename: U
authors.initials: U
authors.lastname: Surti
authors.affiliation: Dept. of Genetics and The Human Genome Institute of New Jersey, Rutgers, The State University of New Jersey.
authors.forename: J
authors.initials: J
authors.lastname: Tischfield
authors.affiliation: Dept. of Genetics and The Human Genome Institute of New Jersey, Rutgers, The State University of New Jersey.
authors.forename: M
authors.initials: M
authors.lastname: Sheldon
authors.affiliation: Dept. of Genetics and The Human Genome Institute of New Jersey, Rutgers, The State University of New Jersey.
authors.forename: J C
authors.initials: JC
authors.lastname: Moore
authors.affiliation: University of Pittsburgh School of Medicine, Dept of Psychiatry.
authors.forename: K
authors.initials: K
authors.lastname: Fish
authors.affiliation: University of Pittsburgh School of Medicine, Dept of Psychiatry ; University of Pittsburgh, Graduate School of Public Health, Department of Human Genetics.
authors.forename: V
authors.initials: V
authors.lastname: Nimgaonkar
keywords: 15q11.2; Autism; Copy Number Variation; Dendritic spine; Dendritogenesis; Induce pluripotent stem cells; Schizophrenia; dendrite; iPSC; intellectual disability