[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-329292-105":59,"doc-detail-329292-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","an-attractor-state-zone-precedes-neural-crest-fate-in-melanoma-initiation","An attractor state zone precedes neural crest fate in melanoma initiation","","The preprint investigates how melanoma initiation emerges from embryonic lineage programs. It reports that single cells within large fields of adjacent abnormal melanocytes reactivate neural crest fate, defining a “cancer precursor zone” with dysplastic morphology, altered gene expression, and aberrant nuclear features. Using single-cell RNA-seq and ATAC-seq, the study identifies a transcriptional attractor state and validates stage-specific initiation signatures in human melanoma.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/an-attractor-state-zone-precedes-neural-crest-fate-in-melanoma-initiation/329292/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/an-attractor-state-zone-precedes-neural-crest-fate-in-melanoma-initiation/329292.png","ImageObject",300,407,{"name":92,"@type":93},"Skyler","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-12","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the “cancer precursor zone” in this study?","Question",{"text":112,"@type":113},"It is a region within adjacent abnormal melanocytes where single cells reactivate neural crest fate, accompanied by aberrant morphology, dysplastic nuclei, and altered gene expression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which molecular regulator is identified as a driver of the cancer precursor zone?",{"text":117,"@type":113},"The study identifies ID1 as a cancer precursor zone driver that binds TCF12 and inhibits downstream targets involved in melanocyte morphology and cell cycle control.",{"name":119,"@type":110,"acceptedAnswer":120},"How do the authors study melanoma initiation at the molecular level?",{"text":121,"@type":113},"They use single-cell RNA-seq and ATAC-seq to define a distinct transcriptional cell attractor state, then validate stage-specific gene expression initiation signatures in human melanoma.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},329292,1790992702,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},2336464648746,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","bioRxiv preprint doi: [https://doi.org/10.1101/2024.10.22.618007](https://doi.org/10.1101/2024.10.22.618007); this version posted October 25, 2024. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \n1 An attractor state zone precedes neural crest fate in melanoma initiation  \n2 Alicia M. McConnell 1,2,3, Maggie H. Chassé 1,2,3, Haley R. Noonan 1,2,3,4, Jeffrey K. Mito 1,2,3,5, 3 Julia Barbano 1, Erika Weiskopf1, Irene F. Gosselink 1, Meera Prasad1,2,3, Song Yang 1,2,3,  \n4 Phammela Abarzua6, Christine G. Lian6, George F. Murphy6, Cole Trapnell7, and Leonard I.  \n5 Zon 1,2,3*  \n6  \n7 1 Stem Cell Program and Division of Hematology/Oncology, Children’s Hospital Boston,  \n8 Howard Hughes Medical Institute, Boston, MA 02115, USA.  \n9 2Harvard Stem Cell Institute, Boston, MA 02115, USA.  \n10 3Harvard Medical School, Boston, MA 02115, USA.  \n11 4Biological and Biomedical Sciences Program, Harvard Medical School, Boston, Massachusetts  \n12 02115, USA.  \n13 5Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02215, USA.  \n14 6Program in Dermatopathology, Department of Pathology, Brigham and Women’s Hospital,  \n15 Boston, MA 02215, USA.  \n16 7Department of Genome Sciences, University of Washington, Seattle, WA, 98195, USA.  \n17 *Corresponding author: [zon@enders.tch.harvard.edu](zon@enders.tch.harvard.edu)  \nbioRxiv preprint doi: [https://doi.org/10.1101/2024.10.22.618007](https://doi.org/10.1101/2024.10.22.618007); this version posted October 25, 2024. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \n18 The field cancerization theory suggests that a group of cells containing oncogenic  \n19 mutations are predisposed to transformation1, 2. We previously identified single cells in  \n20 BRAFV600E;p53-/- zebrafish that reactivate an embryonic neural crest state before initiating  \n21 melanoma3-5. Here we show that single cells reactivate the neural crest fate from within large  \n22 fields of adjacent abnormal melanocytes, which we term the “cancer precursor zone.” These  \n23 cancer precursor zone melanocytes have an aberrant morphology, dysplastic nuclei, and  \n24 altered gene expression. Using single cell RNA-seq and ATAC-seq, we defined a distinct  \n25 transcriptional cell attractor state for cancer precursor zones and validated the stage-specific  \n26 gene expression initiation signatures in human melanoma. We identify the cancer precursor  \n27 zone driver, ID1, which binds to TCF12 and inhibits downstream targets important for the  \n28 maintenance of melanocyte morphology and cell cycle control. Examination of patient  \n29 samples revealed precursor melanocytes expressing ID1, often surrounding invasive  \n30 melanoma, indicating a role for ID1 in early melanomagenesis. This work reveals a  \n31 surprising field effect of melanoma initiation in vivo in which tumors arise from within a  \n32 zone of morphologically distinct, but clinically covert, precursors with altered  \n33 transcriptional fate. Our studies identify novel targets that could improve early diagnosis  \n34 and prevention of melanoma.  \n35 Melanoma incidence has risen sharply over the past 30 years; however multiple studies  \n36 show high disagreement among pathologists in the diagnoses of early potential precursor  \n37 melanocyte lesions6-9. The cancer attractor state theory presented by Stuart Kauffman 50 years ago  \n38 hypothesizes that stable gene expression profiles arise from complex gene expression networks to  \n39 reinforce malignant cell phenotypes10-12. However, due to the difficulty of visualization and  \nbioRxiv preprint doi: [https://doi.org/10.1101/2024.10.22.6180","cbCaioFhQoC77JPJ","https://ap.wps.com/l/cbCaioFhQoC77JPJ","pdf",10466504,49,"English","# Abstract\n## Cancer precursor zone and neural crest fate\n## Single-cell attractor state and driver ID1\n## Field effects and early diagnostic targets","[{\"question\":\"What is the “cancer precursor zone” in this study?\",\"answer\":\"It is a region within adjacent abnormal melanocytes where single cells reactivate neural crest fate, accompanied by aberrant morphology, dysplastic nuclei, and altered gene expression.\"},{\"question\":\"Which molecular regulator is identified as a driver of the cancer precursor zone?\",\"answer\":\"The study identifies ID1 as a cancer precursor zone driver that binds TCF12 and inhibits downstream targets involved in melanocyte morphology and cell cycle control.\"},{\"question\":\"How do the authors study melanoma initiation at the molecular level?\",\"answer\":\"They use single-cell RNA-seq and ATAC-seq to define a distinct transcriptional cell attractor state, then validate stage-specific gene expression initiation signatures in human melanoma.\"}]","An attractor state zone precedes neural crest fate in melanoma initiation | PDF",1789983533,123]