title: Enhanced conversion of induced neuronal cells (iN cells) from human fibroblasts: Utility in uncovering cellular deficits in mental illness-associated chromosomal abnormalities.
abstract: The novel technology of induced neuronal cells (iN cells) is promising for translational neuroscience, as it allows the conversion of human fibroblasts into cells with postmitotic neuronal traits. However, a major technical barrier is the low conversion rate. To overcome this problem, we optimized the conversion media. Using our improved formulation, we studied how major mental illness-associated chromosomal abnormalities may impact the characteristics of iN cells. We demonstrated that our new iN cell culture protocol enabled us to obtain more precise measurement of neuronal cellular phenotypes than previous iN cell methods. Thus, this iN cell culture provides a platform to efficiently obtain possible cellular phenotypes caused by genetic differences, which can be more thoroughly studied in research using other human cell models such as induced pluripotent stem cells.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Passeri
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Wilson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Primerano
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Mari A
authors.initials: MA
authors.lastname: Kondo
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Srona
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Rupali
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Minori
authors.initials: M
authors.lastname: Koga
authors.affiliation: Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Obie
authors.affiliation: Department of Mental Health, Johns Hopkins School of Public Health, 624 N. Broadway, Baltimore, MD 21287, USA.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Zandi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Goes
authors.affiliation: Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: David
authors.initials: D
authors.lastname: Valle
authors.affiliation: NIMH, Branch of Child Psychiatry, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA. Electronic address: asawa1@jhmi.edu.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA. Electronic address: skano2@jhmi.edu.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kano
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA. Electronic address: kishizu2@jhmi.edu.
authors.forename: Koko
authors.initials: K
authors.lastname: Ishizuka
mesh_terms: D000293:Adolescent; D000328:Adult; D001374:Azacitidine / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002869:Chromosome Aberrations; D003470:Culture Media / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D012559:Schizophrenia / Q000235:genetics*; D014635:Valproic Acid / Q000494:pharmacology; D055815:Young Adult
chemical_list: D003470:Culture Media; D006877:Hydroxamic Acids; C012589:trichostatin A; D014635:Valproic Acid; D001374:Azacitidine
keywords: Childhood-onset schizophrenia; Conversion rate; Copy number variations (CNVs); Fibroblasts; Process length; Schizophrenia; Translational research; iN cells