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1. JUMP Cell Painting dataset: morphological impact of 136,000 chemical and genetic perturbations

Author

Srinivas Niranj Chandrasekaran, Jeanelle Ackerman, Eric Alix, D. Michael Ando, John Arevalo, Melissa Bennion, Nicolas Boisseau, Adriana Borowa, Justin D. Boyd, Laurent Brino, Patrick J. Byrne, Hugo Ceulemans, Carolyn Ch’ng, Beth A. Cimini, Djork-Arne Clevert, Nicole Deflaux, John G Doench, Thierry Dorval, Regis Doyonnas, Vincenza Dragone, Ola Engkvist, Patrick W. Faloon, Briana Fritchman, Florian Fuchs, Sakshi Garg, Tamara J. Gilbert, David Glazer, David Gnutt, Amy Goodale, Jeremy Grignard, Judith Guenther, Yu Han, Zahra Hanifehlou, Santosh Hariharan, Desiree Hernandez, Shane R Horman, Gisela Hormel, Michael Huntley, Ilknur Icke, Makiyo Iida, Christina B. Jacob, Steffen Jaensch, Jawahar Khetan, Maria Kost-Alimova, Tomasz Krawiec, Daniel Kuhn, Charles-Hugues Lardeau, Amanda Lembke, Francis Lin, Kevin D. Little, Kenneth R. Lofstrom, Sofia Lotfi, David J. Logan, Yi Luo, Franck Madoux, Paula A. Marin Zapata, Brittany A. Marion, Glynn Martin, Nicola Jane McCarthy, Lewis Mervin, Lisa Miller, Haseeb Mohamed, Tiziana Monteverde, Elizabeth Mouchet, Barbara Nicke, Arnaud Ogier, Anne-Laure Ong, Marc Osterland, Magdalena Otrocka, Pieter J. Peeters, James Pilling, Stefan Prechtl, Chen Qian, Krzysztof Rataj, David E Root, Sylvie K. Sakata, Simon Scrace, Hajime Shimizu, David Simon, Peter Sommer, Craig Spruiell, Iffat Sumia, Susanne E Swalley, Hiroki Terauchi, Amandine Thibaudeau, Amy Unruh, Jelle Van de Waeter, Michiel Van Dyck, Carlo van Staden, Michał Warchoł, Erin Weisbart, Amélie Weiss, Nicolas Wiest-Daessle, Guy Williams, Shan Yu, Bolek Zapiec, Marek Żyła, Shantanu Singh, and Anne E. Carpenter

Abstract

Image-based profiling has emerged as a powerful technology for various steps in basic biological and pharmaceutical discovery, but the community has lacked a large, public reference set of data from chemical and genetic perturbations. Here we present data generated by the Joint Undertaking for Morphological Profiling (JUMP)-Cell Painting Consortium, a collaboration between 10 pharmaceutical companies, six supporting technology companies, and two non-profit partners. When completed, the dataset will contain images and profiles from the Cell Painting assay for over 116,750 unique compounds, over-expression of 12,602 genes, and knockout of 7,975 genes using CRISPR-Cas9, all in human osteosarcoma cells (U2OS). The dataset is estimated to be 115 TB in size and capturing 1.6 billion cells and their single-cell profiles. File quality control and upload is underway and will be completed over the coming months at the Cell Painting Gallery:https://registry.opendata.aws/cellpainting-gallery. A portal to visualize a subset of the data is available athttps://phenaid.ardigen.com/jumpcpexplorer/.

Published
2023
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2. Efficacious intermittent dosing of a novel JAK2 inhibitor in mouse models of polycythemia vera.

Author

Manfred Kraus, Yuxun Wang, Dan Aleksandrowicz, Eric Bachman, Alexander A Szewczak, Deborah Walker, Lin Xu, Melaney Bouthillette, Kaleen M Childers, Brian Dolinski, Andrew M Haidle, Johnny Kopinja, Linda Lee, Jongwon Lim, Kevin D Little, Yanhong Ma, Anjili Mathur, Jan-Rung Mo, Erin O'Hare, Ryan D Otte, Brandon M Taoka, Wenxian Wang, Hong Yin, Anna A Zabierek, Weisheng Zhang, Shuxia Zhao, Joe Zhu, Jonathan R Young, and C Gary Marshall

Subjects
Medicine, Science
Abstract

A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor a Val617→Phe activating mutation in the Janus kinase 2 (JAK2) gene, and both cell culture and mouse models have established a functional role for this mutation in the development of this disease. We describe the properties of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2, that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055 effectively prevented EPO-induced STAT5 activation in the peripheral blood of acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617F-expressing cells from both the spleen and the bone marrow. Using real-time in vivo imaging, we examined the kinetics of disease regression and resurgence, enabling the development of an intermittent dosing schedule that achieved significant reductions in both erythroid and myeloid populations with minimal impact on lymphoid cells. Our studies provide a rationale for the use of non-continuous treatment to provide optimal therapy for PV patients.

Published
2012
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