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Peng, Lee F

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Lee F

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Peng, Lee F

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2009 - 200912010 - 20131

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Author's Publications: search.filters.isAuthorOfPublication.e5c2a1b5-2388-4929-90f5-4a79d8c21cd0

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    A small molecule that directs differentiation of human ESCs into the pancreatic lineage
    (Nature Publishing Group, 2009) Chen, Shuibing; Borowiak, Malgorzata; Maehr, René; Osafune, Kenji; Davidow, Lance; Lam, Kelvin; Peng, Lee F; Schreiber, Stuart; Rubin, Lee; Melton, Douglas
    Stepwise differentiation from embryonic stem cells (ESCs) to functional insulin-secreting beta cells will identify key steps in beta-cell development and may yet prove useful for transplantation therapy for diabetics. An essential step in this schema is the generation of pancreatic progenitors—cells that express Pdx1 and produce all the cell types of the pancreas. High-content chemical screening identified a small molecule, (-)-indolactam V, that induces differentiation of a substantial number of Pdx1-expressing cells from human ESCs. The Pdx1-expressing cells express other pancreatic markers and contribute to endocrine, exocrine and duct cells, in vitro and in vivo. Further analyses showed that (-)-indolactam V works specifically at one stage of pancreatic development, inducing pancreatic progenitors from definitive endoderm. This study describes a chemical screening platform to investigate human ESC differentiation and demonstrates the generation of a cell population that is a key milepost on the path to making beta cells.
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    A TALEN Genome-Editing System for Generating Human Stem Cell-Based Disease Models
    (Elsevier BV, 2013) Ding, Qiurong; Lee, Youn-Kyoung; Schaefer, Esperance; Peters, Derek T.; Veres, Adrian; Kim, Kevin; Kuperwasser, Nicolas; Motola, Daniel L; Meissner, Torsten; Hendriks, William; Trevisan, Marta; Gupta, Rajat; Moisan, Annie; Banks, Eric; Friesen, Max; Schinzel, Robert T.; Xia, Fang; Tang, Alexander; Xia, Yulei; Figueroa, Emmanuel; Wann, Amy; Ahfeldt, Tim; Daheron, Laurence; Zhang, Feng; Rubin, Lee; Peng, Lee F; Chung, Raymond; Musunuru, Kiran; Cowan, Chad
    Transcription activator-like effector nucleases (TALENs) are a new class of engineered nucleases that are easier to design to cleave at desired sites in a genome than previous types of nucleases. We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types. We demonstrate cell-autonomous phenotypes directly linked to disease—dyslipidemia, insulin resistance, hypoglycemia, lipodystrophy, motor-neuron death, and hepatitis C infection. We found little evidence of TALEN off-target effects, but each clonal line nevertheless harbors a significant number of unique mutations. Given the speed and ease with which we were able to derive and characterize these cell lines, we anticipate TALEN-mediated genome editing of human cells becoming a mainstay for the investigation of human biology and disease.