https://m2.mtmt.hu/ hun 2026-05-25 20:04 JournalArticle 34741552 APPROVED true Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada Department of Medicine, Harvard Medical School, Boston, MA, United States Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA, United States Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Department of Bioinformatics, Faculty of Medicine, Semmelweis University, Budapest, 1094, Hungary Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, MA, United States Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States Export Date: 3 June 2024 Correspondence Address: Sethi, N.S.; Department of Medical Oncology, United States; email: nilay_sethi@dfci.harvard.edu Chemicals/CAS: RNA, Guide, CRISPR-Cas Systems Funding details: Harvard Digestive Diseases Center, Harvard University, HDDC Funding details: National Institutes of Health, NIH, P30DK034854 Funding details: National Institutes of Health, NIH Funding details: National Cancer Institute, NCI, NIH 5 P30 CA06516 Funding details: National Cancer Institute, NCI Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, FK142835 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH Funding details: U.S. Department of Defense, DOD, CA201084 Funding details: U.S. Department of Defense, DOD Funding text 1: We thank Jacob Stewart-Ornstein for generously sharing plasmids from which PCR-amplified HDR templates were utilized. We thank Pranshu Sahgal in addition to other Sethi lab members for thoughtful suggestions. Harvard Digestive Disease Center and NIH grant P30DK034854 for core services, resources, technology, and expertise. Dana-Farber/Harvard Cancer Center is supported in part by an NCI Cancer Center Support Grant # NIH 5 P30 CA06516. S.S. was supported by Bolyai (HAS) award and received funding from National Research Development and Innovation Office Hungary (FK142835). P.L. is a recipient of the Prince Mahidol Award Youth Program, Thailand. This work was funded by the Karen Grunebaum Award and Virtual Scholar Award from the Department of Defense (CA201084) to N.S.S and philanthropic support from the Jimmy Fund Walk (Opiela Family), Craig Baskin, and Howard & Wendy Cox to the Sethi Lab. 0 false 2026-05-23T15:54:50.193+0000 2024-04-16T14:08:49.307+0000 2024-03-16T11:24:15.179+0000 true 10034960 Vízkeleti Laura /api/author/10034960 Author true 10034960 2025-08-13T12:35:39.254+0000 Admin 10014568 /api/admin/10014568 Vándor Andrea true 10014568 true 2025-05-07T09:27:03.929+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Spisak, Sandor Identifying regulators of aberrant stem cell and differentiation activity in colorectal cancer using a dual endogenous reporter system true true /api/journal/10015678 REVIEWED true false 10015678 false 10015678 true 2041-1723 Journal FOREIGN 15 1 2230 2230 16 2024 Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators of these key cellular programs, we engineer a dual endogenous reporter system by genome-editing the SOX9 and KRT20 loci of human CRC cell lines to express fluorescent reporters, broadcasting aberrant stem cell-like and differentiation activity, respectively. By applying a CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs to this platform, we identify factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominate 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 and required for in vivo growth of human CRC models. These studies highlight the utility of biologically designed endogenous reporter platforms to uncover regulators with therapeutic potential. 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class="authorship-author-name">Spisák Sándor</span> <span class="authorAux-mtmt"> Molekuláris genetika</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Természettudományi Kutatóközpont">HRN TTK</span>/Molekuláris Élettudományi Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Chen David<sup>*</sup> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Likasitwatanakul Pornlada<sup>*</sup> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Doan Paul<sup>*</sup> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Li Zhixin </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Bala Pratyusha </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10034960"><a href="/gui2/?type=authors&mode=browse&sel=10034960" target="_blank">Vizkeleti Laura (<span class="authorship-author-name">Vízkeleti Laura</span> <span class="authorAux-mtmt"> molekuláris biológia, daganat (epi)genomika</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Bioinformatika Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10082012"><a href="/gui2/?type=authors&mode=browse&sel=10082012" target="_blank">Tisza Viktoria (<span class="authorship-author-name">Tisza Viktoria</span> <span class="authorAux-mtmt"> molekularis biologia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Természettudományi Kutatóközpont">HRN TTK</span>/Molekuláris Élettudományi Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >De Silva Pushpamali </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Giannakis Marios </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Wolpin Brian </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Qi Jun </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Sethi Nilay S. ✉ </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;34741552" target="_blank">Identifying regulators of aberrant stem cell and differentiation activity in colorectal cancer using a dual endogenous reporter system</a></div> <div> <span class="journal-title">NATURE COMMUNICATIONS</span> <span class="journal-issn">( <a target="_blank" href="https://portal.issn.org/resource/ISSN/2041-1723">2041-1723</a>)</span>: <span class="journal-volume">15</span> <span class="journal-issue">1</span> <span class="page"> Paper 2230. 16 p. </span> <span class="year">(2024)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1038/s41467-024-46285-w" target="_blank" href="https://doi.org/10.1038/s41467-024-46285-w"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001185523200024" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001185523200024"> WoS </a> </span> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:black" title="206463" target="_blank" href="http://real.mtak.hu/206463"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85187639524" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85187639524"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="38472198" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=38472198&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Biochemistry, Genetics and Molecular Biology (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Chemistry (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Physics and Astronomy (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Regionális Tudományok Bizottsága IXGJO RTB [1901-]&nbsp;&nbsp;&nbsp;A nemzetközi</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 9</span> | Független: 8 | Függő: 1 | Nem jelölt: 0 | WoS jelölt: 8 | Scopus jelölt:&nbsp;5 | WoS/Scopus jelölt:&nbsp;8 | DOI jelölt:&nbsp;9 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;34741552&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 2 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 34741552</span> | <span class="status-data status-APPROVED"> Nyilvános </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (FK142835) </div> <div class="lastModified">Utolsó módosítás: 2024.04.16. 16:08 Sonnevend Kinga (SE_AOK_Adm5_Élet_kutcsop, admin) </div> <div class="lockedBy">Központi kezelésű 2025.05.07. 11:27 Vándor Andrea (VA, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada Department of Medicine, Harvard Medical School, Boston, MA, Uni...</pre> </div></div>