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Findings reveal four distinct spatial compartments with functional diversity, highlight a Ki67+ proliferative population as a key driver of luminal B-like features, and connect gene signatures with clinical outcomes.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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experimental approaches were used to define molecular features in ER+ luminal breast cancer?","Question",{"text":63,"@type":64},"Spatial transcriptomics and single-cell RNA-sequencing were applied to patient-derived xenografts, with additional validation using single-cell analyses and protein-based dual immunohistochemistry.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How many spatial compartments were identified within ER+ breast cancers?",{"text":68,"@type":64},"Four spatially distinct compartments were identified, including oestrogen-responsive, proliferative, hypoxia-induced, and inflammation-related populations.",{"name":70,"@type":61,"acceptedAnswer":71},"Which cell population was crucial for oestrogen-dependent tumour growth and luminal B-like features?",{"text":72,"@type":64},"The Ki67+ proliferative population, rather than the oestrogen-responsive compartment, was crucial for oestrogen-dependent tumour growth and acquisition of luminal B-like 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\nMolecular features of luminal breast cancer defined through spatial and single-cell transcriptomics  \nRyohei Yoshitake1 Xiaoqiang Wang1  \n Hitomi Mori1,2  Kohei Saeki1, 4  \nDesiree Ha1  Gregory Chang1  \nXiwei Wu3  Jinhui Wang3  Hyun Jeong Shim1   \nYin Chan1  Shiuan Chen1   \n1 Department of Cancer Biology and Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA  \n2 Department of Surgery and Oncology, Graduate School of Medicine, Kyushu University, Fukuoka, Japan  \n3 Integrative Genomics Core, Beckman Research Institute of City of Hope, Monrovia, California, USA  \n4 Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan  \nCorrespondence  \nShiuanChen, Department of Cancer Biology and Molecular Medicine, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA. [Email:](Email: SChen@coh.org)[ SChen@coh.org](Email: SChen@coh.org)  \nGraphical Abstract  \nOur space-gene-function study revealed four spatially distinct populations within ER+ breast cancers. These populations showed functional diversity (oestrogen-responsive, proliferative, hypoxia-induced, and inflammationrelated) . The ‘proliferative’ population, rather than the ‘oestrogen-responsive’population, was crucial for oestrogen-dependent tumour growth, leading to the acquisition of luminal B-like features.  \nClin. Transl. Med. 2024;14:e1548 .  \n[https://doi.org/10.1002/ctm2.1548](https://doi.org/10.1002/ctm2.1548)  \n[wileyonlinelibrary.com/journal/ctm2](wileyonlinelibrary.com/journal/ctm2)  \nDOI: 10.1002/ctm2.1548  \nRESEARCH ARTICLE  \nMolecular features of luminal breast cancer defined through spatial and single-cell transcriptomics  \nRyohei Yoshitake1 Xiaoqiang Wang1  \n Hitomi Mori1,2  Kohei Saeki1, 4  \nDesiree Ha1  Gregory Chang1  \nXiwei Wu3  Jinhui Wang3  Hyun Jeong Shim1   \nYin Chan1  Shiuan Chen1   \n1 Department of Cancer Biology and Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA  \n2 Department of Surgery and Oncology, Graduate School of Medicine, Kyushu University, Fukuoka, Japan  \n3 Integrative Genomics Core, Beckman Research Institute of City of Hope, Monrovia, California, USA  \n4 Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan  \nCorrespondence  \nShiuan Chen, Department of Cancer Biology and Molecular Medicine, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.  \nEmail: [SChen@coh.org](SChen@coh.org)  \nFunding information  \nLester M. and Irene C. Finkelstein endowment; NIH, Grant/Award Numbers: U01ES026137, P30CA033572  \nAbstract  \nBackground: Intratumour heterogeneity is a hallmark of most solid tumours, including breast cancers. We applied spatial transcriptomics and single-cell RNA-sequencing on patient-derived xenografts (PDXs) to profile spatially resolved cell populations within oestrogen receptor-positive (ER+ )breast cancer and to elucidate their importance in oestrogen-dependent tumour growth. Methods: Two PDXs of ‘ER-high’ breast cancers with opposite oestrogenmediated growth responses were investigated: oestrogen-suppressed GS3 (80– 100% ER) and oestrogen-dependent SC31 (40–90% ER) models. The observation was validated via single-cell analyses on an ‘ER-low’ PDX, GS1 (5% ER) . The results from our spatial and single-cell analyses were further supported by a public ER+ breast cancer single-cell dataset and protein-based dual immunohistochemistry (IHC) of SC31 examining important luminal cancer markers (i.e., ER, progesterone receptor and Ki67) . The translational implication of our findings was assessed by clinical outcome analyses on publicly available cohorts. Results: Our space-gene-function study revealed four spatially distinct compartments within ER+ breast cancers. These compartments showed functional diversity (oestrogen-responsive, proliferative, hypoxia-induced and inflammationrelated) . The ‘pr","cbCaijIkgtBz7C1n","https://ap.wps.com/l/cbCaijIkgtBz7C1n","pdf",14300302,23,"English","# Abstract\n## Background and Methods\n## Results\n## Conclusions\n# Key Words\n# Background","[{\"question\":\"What experimental approaches were used to define molecular features in ER+ luminal breast cancer?\",\"answer\":\"Spatial transcriptomics and single-cell RNA-sequencing were applied to patient-derived xenografts, with additional validation using single-cell analyses and protein-based dual immunohistochemistry.\"},{\"question\":\"How many spatial compartments were identified within ER+ breast cancers?\",\"answer\":\"Four spatially distinct compartments were identified, including oestrogen-responsive, proliferative, hypoxia-induced, and inflammation-related populations.\"},{\"question\":\"Which cell population was crucial for oestrogen-dependent tumour growth and luminal B-like features?\",\"answer\":\"The Ki67+ proliferative population, rather than the oestrogen-responsive compartment, was crucial for oestrogen-dependent tumour growth and acquisition of luminal B-like features.\"}]","Molecular features of luminal breast cancer defined through spatial and single-cell transcriptomics | PDF",1789975527,58]