MISpheroID: a knowledgebase and transparency tool for minimum information in spheroid identity

Spheroids are three-dimensional cellular models with widespread basic and translational application across academia and industry. However, methodological transparency and guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,058 published spheroid-related experiments. Interrogation of this knowledgebase identified heterogeneity in the methodological setup of spheroids. Empirical evaluation and interlaboratory validation of selected variations in spheroid methodology revealed diverse impacts on spheroid metrics. To facilitate interpretation, stimulate transparency and increase awareness, the Consortium defines the MISpheroID string, a minimum set of experimental parameters required to report spheroid research. Thus, MISpheroID combines a valuable resource and a tool for three-dimensional cellular models to mine experimental parameters and to improve reproducibility. © 2021, The Author(s)

High Throughput FISH Screening Identifies Small Molecules That Modulate Oncogenic lncRNA MALAT1 via GSK3B and hnRNPs

Traditionally, small molecule-based drug discovery has mainly focused on proteins as the drug target. Opening RNA as an additional target space for small molecules offers the possibility to therapeutically modulate disease-driving non-coding RNA targets as well as mRNA of otherwise undruggable protein targets. MALAT1 is a highly conserved long-noncoding RNA whose overexpression correlates with poor overall patient survival in some cancers. We report here a fluorescence in-situ hybridization-based high-content imaging screen to identify small molecules that modulate the oncogenic lncRNA MALAT1 in a cellular setting. From a library of FDA approved drugs and known bioactive molecules, we identified two compounds, including Niclosamide, an FDA-approved drug, that lead to a rapid decrease of MALAT1 nuclear levels with good potency. Mode-of-action studies suggest a novel cellular regulatory pathway that impacts MALAT1 lncRNA nuclear levels by GSK3B activation and the involvement of the RNA modulating family of heterogenous nuclear ribonucleoproteins (hnRNPs). This study is the basis for the identification of novel targets that lead to a reduction of the oncogenic lncRNA MALAT1 in a cancer setting

MISpheroID: a knowledgebase and transparency tool for minimum information in spheroid identity

none51siSpheroids are three-dimensional cellular models with widespread basic and translational application across academia and industry. However, methodological transparency and guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,058 published spheroid-related experiments. Interrogation of this knowledgebase identified heterogeneity in the methodological setup of spheroids. Empirical evaluation and interlaboratory validation of selected variations in spheroid methodology revealed diverse impacts on spheroid metrics. To facilitate interpretation, stimulate transparency and increase awareness, the Consortium defines the MISpheroID string, a minimum set of experimental parameters required to report spheroid research. Thus, MISpheroID combines a valuable resource and a tool for three-dimensional cellular models to mine experimental parameters and to improve reproducibility.openPeirsman A.; Blondeel E.; Ahmed T.; Anckaert J.; Audenaert D.; Boterberg T.; Buzas K.; Carragher N.; Castellani G.; Castro F.; Dangles-Marie V.; Dawson J.; De Tullio P.; De Vlieghere E.; Dedeyne S.; Depypere H.; Diosdi A.; Dmitriev R.I.; Dolznig H.; Fischer S.; Gespach C.; Goossens V.; Heino J.; Hendrix A.; Horvath P.; Kunz-Schughart L.A.; Maes S.; Mangodt C.; Mestdagh P.; Michlikova S.; Oliveira M.J.; Pampaloni F.; Piccinini F.; Pinheiro C.; Rahn J.; Robbins S.M.; Siljamaki E.; Steigemann P.; Sys G.; Takayama S.; Tesei A.; Tulkens J.; Van Waeyenberge M.; Vandesompele J.; Wagemans G.; Weindorfer C.; Yigit N.; Zablowsky N.; Zanoni M.; Blondeel P.; De Wever O.Peirsman A.; Blondeel E.; Ahmed T.; Anckaert J.; Audenaert D.; Boterberg T.; Buzas K.; Carragher N.; Castellani G.; Castro F.; Dangles-Marie V.; Dawson J.; De Tullio P.; De Vlieghere E.; Dedeyne S.; Depypere H.; Diosdi A.; Dmitriev R.I.; Dolznig H.; Fischer S.; Gespach C.; Goossens V.; Heino J.; Hendrix A.; Horvath P.; Kunz-Schughart L.A.; Maes S.; Mangodt C.; Mestdagh P.; Michlikova S.; Oliveira M.J.; Pampaloni F.; Piccinini F.; Pinheiro C.; Rahn J.; Robbins S.M.; Siljamaki E.; Steigemann P.; Sys G.; Takayama S.; Tesei A.; Tulkens J.; Van Waeyenberge M.; Vandesompele J.; Wagemans G.; Weindorfer C.; Yigit N.; Zablowsky N.; Zanoni M.; Blondeel P.; De Wever O