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Genome-Scale CRISPR Screening Identifies Novel Human Pluripotent Gene Networks

55 Pages Posted: 6 Jun 2018 Sneak Peek Status: Review Complete

See all articles by Robert J. Ihry

Robert J. Ihry

Novartis Institutes for Biomedical Research - Department of Neuroscience

Max Salick

Novartis Institutes for Biomedical Research - Department of Neuroscience

Daniel J. Ho

Novartis Institutes for Biomedical Research - Department of Neuroscience

Marie Sondey

Novartis Institutes for Biomedical Research - Department of Neuroscience

Sravya Kommineni

Novartis Institutes for Biomedical Research - Department of Neuroscience

Steven Paula

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

Joe Raymond

Novartis Institutes for Biomedical Research - Department of Neuroscience

Elizabeth Frias

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

Kathleen Worringer

Novartis Institutes for Biomedical Research - Department of Neuroscience

Carsten Russ

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

John Reece-Hoyes

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

Bob Altshuler

Novartis Institutes for Biomedical Research - Department of Neuroscience

Ranjit Randhawa

Novartis Institutes for Biomedical Research - Department of Neuroscience

Zinger Yang

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

Gregory McAllister

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

Gregory R. Hoffman

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

Ricardo Dolmetsch

Novartis Institutes for Biomedical Research - Department of Neuroscience

Ajamete Kaykas

Novartis Institutes for Biomedical Research - Department of Neuroscience

More...

Abstract

Human pluripotent stem cells (hPSCs) generate a wide variety of disease-relevant cells that can be used to improve the translation of preclinical research. Despite the potential of hPSCs, their use for genetic screening has been limited because of technical challenges. We developed a renewable Cas9/sgRNA-hPSC library where loss-of-function mutations can be induced at will. Our inducible-mutant hPSC library can be used for an unlimited number of genome-wide screens. We screened for novel genes involved in 3 of the fundamental properties of hPSCs: Their ability to self-renew/survive, their capacity to differentiate into somatic cells, and their inability to survive as single-cell clones. We identified a plethora of novel genes with unidentified roles in hPSCs. These results are available as a resource for the community to increase the understanding of both human development and genetics. In the future, our stem cell library approach will be a powerful tool to identify disease-modifying genes.

Suggested Citation

Ihry, Robert J. and Salick, Max and Ho, Daniel J. and Sondey, Marie and Kommineni, Sravya and Paula, Steven and Raymond, Joe and Frias, Elizabeth and Worringer, Kathleen and Russ, Carsten and Reece-Hoyes, John and Altshuler, Bob and Randhawa, Ranjit and Yang, Zinger and McAllister, Gregory and Hoffman, Gregory R. and Dolmetsch, Ricardo and Kaykas, Ajamete, Genome-Scale CRISPR Screening Identifies Novel Human Pluripotent Gene Networks (2018). Available at SSRN: https://ssrn.com/abstract=3189387 or http://dx.doi.org/10.2139/ssrn.3189387
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Robert J. Ihry (Contact Author)

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Max Salick

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Daniel J. Ho

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Marie Sondey

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Sravya Kommineni

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Steven Paula

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Joe Raymond

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Elizabeth Frias

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Kathleen Worringer

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Carsten Russ

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

John Reece-Hoyes

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Bob Altshuler

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Ranjit Randhawa

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Zinger Yang

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Gregory McAllister

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Gregory R. Hoffman

Novartis Institutes for Biomedical Research - Department of Chemical Biology and Therapeutics

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Ricardo Dolmetsch

Novartis Institutes for Biomedical Research - Department of Neuroscience

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

Ajamete Kaykas

Novartis Institutes for Biomedical Research - Department of Neuroscience ( email )

250 Massachusetts Avenue
6A-209
Cambridge, MA 02139
United States

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