Search Results

Luminescent peptide tagging enables efficient screening for CRISPR-mediated knock-in in human induced pluripotent stem cells

Human pluripotent stem cells are increasingly used for CRISPR-mediated gene targeting in efforts to generate models of human diseases. This is a challenging task because of the high sensitivity of these cells to suboptimal conditions, including...

Authors: Madsen RR, Semple RK

NK cells switch from granzyme B to death receptor-mediated cytotoxicity during serial killing.

NK cells eliminate virus-infected and tumor cells by releasing cytotoxic granules containing granzyme B (GrzB) or by engaging death receptors that initiate caspase cascades. The orchestrated interplay between both cell death pathways remains poorly...

Authors: Prager I, Liesche C, van Ooijen H, Urlaub D, Verron Q, Sandström N, Fasbender F, Claus M, Eils R,...

A High-Throughput Platform to Identify Small-Molecule Inhibitors of CRISPR-Cas9

The precise control of CRISPR-Cas9 activity is required for a number of genome engineering technologies. Here, we report a generalizable platform that provided the first synthetic small-molecule inhibitors of Streptococcus pyogenes Cas9 (SpCas9) that...

Authors: Maji B, Gangopadhyay SA, Lee M, Shi M, Wu P, Heler R, Mok B, Lim D, Siriwardena SU, Paul B, Dancík...

Functionality of Primary Hepatic Non-Parenchymal Cells in a 3D Spheroid Model and Contribution to Acetaminophen Hepatotoxicity

In addition to hepatocytes, the liver comprises a host of specialised non-parenchymal cells which are important to consider in the development of in vitro models which are both physiologically and toxicologically relevant. We have characterized...

Authors: Catherine C Bell , Bhavik Chouhan , Linda C Andersson , Håkan Andersson , James W Dear , Dominic P...

SST Peer Reviewed

Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1

Targeted genome editing in hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematological diseases. However, the limited efficiency of homology-directed editing in primitive HSPCs constrains the yield of...

Authors: Schiroli G, Ferrari S, Conway A, Jacob A, Capo V, Albano L, Plati T, Castiello MC, Sanvito F,...

Stem cell-derived polarized hepatocytes

Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver biology. Despite their numerous advantages, HLCs lack critical in vivo characteristics, including cell polarity. Here, we report a stem cell...

Authors: Viet Loan Dao Thi, Xianfang Wu, Rachel L. Belote, Ursula Andreo, Constantin N. Takacs, Joseph P....

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms

SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor...

Authors: Ye Wang , Morvarid Mohseni , Angelo Grauel , Javier Estrada Diez , Wei Guan , Simon Liang , Jiyoung...

Distinct Mitochondrial Defects Trigger the Integrated Stress Response Depending on the Metabolic State of the Cell

Mitochondrial dysfunction is associated with activation of the integrated stress response (ISR) but the underlying triggers remain unclear. We systematically combined acute mitochondrial inhibitors with genetic tools for compartment-specific NADH...

Authors: Eran Mick, Denis V Titov, Owen S Skinner, Rohit Sharma, Alexis A Jourdain, Vamsi K Mootha

Setup of human liver-chips integrating 3D models, microwells and a standardized microfluidic platform as proof-of-concept study to support drug evaluation

Human 3D liver microtissues/spheroids are powerful in vitro models to study drug-induced liver injury (DILI) but the small number of cells per spheroid limits the models’ usefulness to study drug metabolism. In this work, we scale up the number of...

Authors: Benoit Cox, Patrick Barton , Reiner Class, Hannah Coxhead, Claude Delatour , Eric Gillent , Jamie...

CRISPR off-target detection with DISCOVER-seq

DISCOVER-seq (discovery of in situ Cas off-targets and verification by sequencing) is a broadly applicable approach for unbiased CRISPR-Cas off-target identification in cells and tissues. It leverages the recruitment of DNA repair factors to...

Authors: Wienert B, Wyman SK, Yeh CD, Conklin BR, Corn JE

SST Peer Reviewed

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