Sandor Spisak, David Chen, Pornlada Likasitwatanakul, Paul Doan, Zhixin Li, Pratyusha Bala, Laura Vizkeleti, Viktoria Tisza, Pushpamail De Silva, Marios Giannakis, Brian Wolpin, Jun Qi, Nilay S Sethi
{"title":"Utilizing a dual endogenous reporter system to identify functional regulators of aberrant stem cell and differentiation activity in colorectal cancer.","authors":"Sandor Spisak, David Chen, Pornlada Likasitwatanakul, Paul Doan, Zhixin Li, Pratyusha Bala, Laura Vizkeleti, Viktoria Tisza, Pushpamail De Silva, Marios Giannakis, Brian Wolpin, Jun Qi, Nilay S Sethi","doi":"10.1101/2023.06.21.545895","DOIUrl":"10.1101/2023.06.21.545895","url":null,"abstract":"<p><p>Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators that regulate these key cellular programs in CRC, we developed an endogenous reporter system by genome-editing human CRC cell lines with knock-in fluorescent reporters at the SOX9 and KRT20 locus to report aberrant stem cell-like activity and differentiation, respectively, and then performed pooled genetic perturbation screens. Constructing a dual reporter system that simultaneously monitored aberrant stem cell-like and differentiation activity in the same CRC cell line improved our signal to noise discrimination. Using a focused-library CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs, we identified factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominated SMARCB1 of the BAF complex (also known as SWI/SNF) as a negative regulator of differentiation across an array of neoplastic colon models. SMARCB1 is a dependency in CRC and required for <i>in vivo</i> growth of human CRC models. These studies highlight the utility of a biologically designed endogenous reporter system to uncover novel therapeutic targets for drug development.</p>","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81265723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stability Results for a System of Nonlinear Viscoelastic Plate Equations with Nonlinear Frictional Damping and Logarithmic Source Terms","authors":"Mohammad M. Algharabli","doi":"10.1007/s10883-023-09676-8","DOIUrl":"https://doi.org/10.1007/s10883-023-09676-8","url":null,"abstract":"","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"60 20","pages":""},"PeriodicalIF":0.9,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139381651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stabilization of the Viscoelastic Wave Equation with Variable Coefficients and a Delay Term in Nonlocal Boundary Feedback","authors":"Sheng-Jie Li, Shugen Chai","doi":"10.1007/s10883-023-09673-x","DOIUrl":"https://doi.org/10.1007/s10883-023-09673-x","url":null,"abstract":"","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"6 6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139389554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Linear Control Systems on Homogeneous Spaces of the Heisenberg Group","authors":"Adriano Da Silva, Eyüp Kizil, Okan Duman","doi":"10.1007/s10883-023-09670-0","DOIUrl":"https://doi.org/10.1007/s10883-023-09670-0","url":null,"abstract":"","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"56 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135476481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stability of Geometric Separating Flows","authors":"K. Lee, T. Nguyen, A. Rojas","doi":"10.1007/s10883-023-09669-7","DOIUrl":"https://doi.org/10.1007/s10883-023-09669-7","url":null,"abstract":"","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135993633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Existence and Exponential Stabilization of an Axial Vibrations Cable with Time-Varying Length","authors":"Billal Lekdim, Ammar Khemmoudj","doi":"10.1007/s10883-023-09650-4","DOIUrl":"https://doi.org/10.1007/s10883-023-09650-4","url":null,"abstract":"","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136013237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Existence of Robust Non-Uniformly Hyperbolic Endomorphism in Homotopy Classes","authors":"Victor Janeiro","doi":"10.1007/s10883-023-09668-8","DOIUrl":"https://doi.org/10.1007/s10883-023-09668-8","url":null,"abstract":"","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135095331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conic Nonholonomic Constraints on Surfaces and Control Systems","authors":"Timothée Schmoderer, Witold Respondek","doi":"10.1007/s10883-023-09659-9","DOIUrl":"https://doi.org/10.1007/s10883-023-09659-9","url":null,"abstract":"This paper addresses the equivalence problem of conic submanifolds in the tangent bundle of a smooth 2-dimensional manifold. Those are given by a quadratic relation between the velocities and are treated as nonholonomic constraints whose admissible curves are trajectories of the corresponding control systems, called quadratic systems. We deal with the problem of characterising and classifying conic submanifolds under the prism of feedback equivalence of control systems, both control-affine and fully nonlinear. The first main result of this work is a complete description of non-degenerate conic submanifolds via a characterisation under feedback transformations of the novel class of quadratic control-affine systems. This characterisation can explicitly be tested on structure functions defined for any control-affine system and gives a normal form of quadratisable systems and of conic submanifolds. Then, we consider the classification problem of regular conic submanifolds (ellipses, hyperbolas, and parabolas), which is treated via feedback classification of quadratic control-nonlinear systems. Our classification includes several normal forms of quadratic systems (in particular, normal forms not containing functional parameters as well as those containing neither functional nor real parameters) and, as a consequence, gives a classification of regular conic submanifolds.","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135131720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Víctor Ayala, Adriano Da Silva, Alejandro Otero Robles
{"title":"Dynamics of Linear Control Systems on the Group of Proper Motions","authors":"Víctor Ayala, Adriano Da Silva, Alejandro Otero Robles","doi":"10.1007/s10883-023-09667-9","DOIUrl":"https://doi.org/10.1007/s10883-023-09667-9","url":null,"abstract":"","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"66 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135815573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conditions for Atomic Disintegration to be Monoatomic","authors":"Simeão Targino da Silva, Régis Varão","doi":"10.1007/s10883-023-09665-x","DOIUrl":"https://doi.org/10.1007/s10883-023-09665-x","url":null,"abstract":"","PeriodicalId":54847,"journal":{"name":"Journal of Dynamical and Control Systems","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136060074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}