title: Modeling anorexia nervosa: transcriptional insights from human iPSC-derived neurons.
abstract: Anorexia nervosa (AN) is a complex and multifactorial disorder occurring predominantly in women. Despite having the highest mortality among psychiatric conditions, it still lacks robust and effective treatment. Disorders such as AN are most likely syndromes with multiple genetic contributions, however, genome-wide studies have been underpowered to reveal associations with this uncommon illness. Here, we generated induced pluripotent stem cells (iPSCs) from adolescent females with AN and unaffected controls. These iPSCs were differentiated into neural cultures and subjected to extensive transcriptome analysis. Within a small cohort of patients who presented for treatment, we identified a novel gene that appears to contribute to AN pathophysiology, TACR1 (tachykinin 1 receptor). The participation of tachykinins in a variety of biological processes and their interactions with other neurotransmitters suggest novel mechanisms for how a disrupted tachykinin system might contribute to AN symptoms. Although TACR1 has been associated with psychiatric conditions, especially anxiety disorders, we believe this report is its first association with AN. Moreover, our human iPSC approach is a proof-of-concept that AN can be modeled in vitro with a full human genetic complement, and represents a new tool for understanding the elusive molecular and cellular mechanisms underlying the disease.
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Negraes
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Cugola
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.|Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.
authors.forename: R H
authors.initials: RH
authors.lastname: Herai
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Trujillo
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: A S
authors.initials: AS
authors.lastname: Cristino
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.|National Center for Genetic Engineering and Biotechnology, Virology and Cell Technology Laboratory, Pathum Thani, Thailand.
authors.forename: T
authors.initials: T
authors.lastname: Chailangkarn
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Muotri
authors.affiliation: Department of Pediatrics and Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Duvvuri
mesh_terms: D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000235:genetics*
chemical_list: D018040:Receptors, Neurokinin-1