A resource of induced pluripotent stem cell (iPSC) lines including clinical, genomic, and cellular data from genetically isolated families with mood and psychotic disorders.
Sevilla D Detera-WadleighLayla KassemEmily BesanconFabiana L LopesNirmala AkulaHeejong SungMeghan BlattnerLaura SheridanLey Nadine LacbawanJoshua GarciaFrancis GordovezKatherine HoseyCassandra DonnerClaudio SalviniThomas SchulzeDavid T W ChenBryce EnglandJoanna CrossXueying JiangWinston CoronaJill RussBarbara MallonAmalia DutraEvgenia PakJoe SteinerNasir MalikTheresa de GuzmanNatia HoratoMariana B MallmannVictoria MendesAmanda L DűckAntonio Egidio NardiFrancis J McMahonPublished in: Translational psychiatry (2023)
Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics. Here we report the creation and availability of an iPSC resource comprising clinical, genomic, and cellular data obtained from genetically isolated families with BD and related conditions. Results from the first 324 study participants, 61 of whom have validated pluripotent clones, show enrichment of rare single nucleotide variants and CNVs overlapping many known risk genes and pathogenic CNVs. This growing iPSC resource is available to scientists pursuing functional genomic studies of BD and related conditions.
Keyphrases
- induced pluripotent stem cells
- copy number
- bipolar disorder
- major depressive disorder
- genome wide
- mitochondrial dna
- induced apoptosis
- dna methylation
- cell cycle arrest
- stem cells
- endothelial cells
- small molecule
- signaling pathway
- cell death
- depressive symptoms
- gene expression
- machine learning
- endoplasmic reticulum stress
- oxidative stress
- genome wide identification
- mesenchymal stem cells
- mental health
- dna damage
- multiple sclerosis
- dna repair
- cell proliferation
- case control
- drug induced