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Stem Cell Reports. 2017 Mar 14;8(3):519-528. doi: 10.1016/j.stemcr.2017.01.010. Epub 2017 Feb 16.

Divergent Levels of Marker Chromosomes in an hiPSC-Based Model of Psychosis.

Author information

1
Departments of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
2
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: cfonseca@bcm.edu.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
4
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
5
F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
6
Departments of Psychiatry, Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
7
Department of Internal Medicine, McLean Hospital, Belmont, MA 02478, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
8
Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
9
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
10
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA; Psychology Research Laboratory, McLean Hospital, Belmont, MA 02478, USA. Electronic address: dlevy@mclean.harvard.edu.
11
Departments of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA. Electronic address: kristen.brennand@mssm.edu.

Abstract

In the process of generating presumably clonal human induced pluripotent stem cells (hiPSCs) from two carriers of a complex structural rearrangement, each having a psychotic disorder, we also serendipitously generated isogenic non-carrier control hiPSCs, finding that the rearrangement occurs as an extrachromosomal marker (mar) element. All confirmed carrier hiPSCs and differentiated neural progenitor cell lines were found to be mosaic. We caution that mar elements may be difficult to functionally evaluate in hiPSC cultures using currently available methods, as it is difficult to distinguish cells with and without mar elements in live mosaic cultures.

KEYWORDS:

9p24.1; bipolar disorder; human induced pluripotent stem cell; isogenic; marker chromosome; mosaic; neural progenitor cell; schizophrenia

PMID:
28216146
PMCID:
PMC5355568
DOI:
10.1016/j.stemcr.2017.01.010
[Indexed for MEDLINE]
Free PMC Article

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