title: Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells.
abstract: Induced pluripotent stem cells (iPSCs) are an essential tool for modeling how causal genetic variants impact cellular function in disease, as well as an emerging source of tissue for regenerative medicine. The preparation of somatic cells, their reprogramming and the subsequent verification of iPSC pluripotency are laborious, manual processes limiting the scale and reproducibility of this technology. Here we describe a modular, robotic platform for iPSC reprogramming enabling automated, high-throughput conversion of skin biopsies into iPSCs and differentiated cells with minimal manual intervention. We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCs. These lines display less line-to-line variation than either manually produced lines or lines produced through automation followed by single-colony subcloning. The robotic platform we describe will enable the application of iPSCs to population-scale biomedical problems including the study of complex genetic diseases and the development of personalized medicines.
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Paull
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Sevilla
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Aana Kim
authors.initials: AK
authors.lastname: Hahn
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Hesed
authors.initials: H
authors.lastname: Kim
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Napolitano
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, USA.|The Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tsankov
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Linshan
authors.initials: L
authors.lastname: Shang
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Krumholz
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Premlatha
authors.initials: P
authors.lastname: Jagadeesan
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Woodard
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Sun
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.|Division of Medical Genomics, Inova Translational Medicine Institute, Inova Health System, Falls Church, Virginia, USA.
authors.forename: Thierry
authors.initials: T
authors.lastname: Vilboux
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Zimmer
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Eliana
authors.initials: E
authors.lastname: Forero
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Dorota N
authors.initials: DN
authors.lastname: Moroziewicz
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Hector
authors.initials: H
authors.lastname: Martinez
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: May Christine V
authors.initials: MC
authors.lastname: Malicdan
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Keren A
authors.initials: KA
authors.lastname: Weiss
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Vensand
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Dusenberry
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Polus
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Karla Therese L
authors.initials: KT
authors.lastname: Sy
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kahler
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.|NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institute of Health and National Human Genome Research Institute, National Institute of Health, Bethesda, Maryland, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Solomon
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chang
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, USA.|The Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, USA.|The Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.|The Howard Hughes Medical Institute, Cambridge, Massachusetts, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Eggan
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, New York, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Noggle
mesh_terms: D061249:Batch Cell Culture Techniques / Q000295:instrumentation*; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation / Q000295:instrumentation*; D002478:Cells, Cultured; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D012371:Robotics / Q000295:instrumentation*