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Fang, Rongxin

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Fang

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Rongxin

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Fang, Rongxin

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Author's Publications: search.filters.isAuthorOfPublication.c758ed5d-b327-40af-9b50-74f27c75e09f

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    Subclonal Cooperation Drives Metastasis by Modulating Local and Systemic Immune Microenvironments
    (Springer Science and Business Media LLC, 2019-07) Cristea, Simona; Kwak, Minsuk; Qin, Yuanbo; Laszewski, Tyler; Luoma, Adrienne; Marusyk, Andriy; Wagle, Nikhil; Fang, Rongxin; Polyak, Kornelia; Janiszewska, Michalina; Tabassum, Doris; Castaño, Zafira; Yamamoto, Kimiyo; Kingston, Natalie; Murphy, Katherine; Shu, Shaokun; Harper, Nicholas; Gil del Alcazar, Carlos; Alečković, Maša; Ekram, Muhammad; Cohen, Ofir; Wucherpfennig, Kai; Michor, Franziska; McAllister, Sandra
    Most human tumours are heterogeneous, composed of cellular clones with different properties present at variable frequencies. Highly heterogeneous tumours have poor clinical outcomes, yet the underlying mechanism remains poorly understood. Here, we show that minor subclones of breast cancer cells expressing IL11 and FIGF (VEGFD) cooperate to promote metastatic progression and generate polyclonal metastases composed of driver and neutral subclones. Expression profiling of the epithelial and stromal compartments of monoclonal and polyclonal primary and metastatic lesions revealed that this cooperation is indirect, mediated through the local and systemic microenvironments. We identified neutrophils as a leukocyte population stimulated by the IL11-expressing minor subclone and showed that the depletion of neutrophils prevents metastatic outgrowth. Single-cell RNA-seq of CD45+ cell populations from primary tumours, blood and lungs demonstrated that IL11 acts on bone-marrow-derived mesenchymal stromal cells, which induce pro-tumorigenic and pro-metastatic neutrophils. Our results indicate key roles for non-cell-autonomous drivers and minor subclones in metastasis.
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    Conservation and divergence of cortical cell organization in human and mouse revealed by MERFISH
    (American Association for the Advancement of Science (AAAS), 2022-07) Fang, Rongxin; Xia, Chenglong; Close, Jennie L.; Zhang, Meng; He, Jiang; Huang, Zhengkai; Halpern, Aaron R.; Long, Brian; Miller, Jeremy A.; Lein, Ed S.; Zhuang, Xiaowei
    The human cerebral cortex has tremendous cellular diversity. How different cell types are organized in the human cortex and how cellular organization varies across species remain unclear. In this study, we performed spatially resolved single-cell profiling of 4000 genes using multiplexed error-robust fluorescence in situ hybridization (MERFISH), identified more than 100 transcriptionally distinct cell populations, and generated a molecularly defined and spatially resolved cell atlas of the human middle and superior temporal gyrus. We further explored cell-cell interactions arising from soma contact or proximity in a cell type–specific manner. Comparison of the human and mouse cortices showed conservation in the laminar organization of cells and differences in somatic interactions across species. Our data revealed human-specific cell-cell proximity patterns and a markedly increased enrichment for interactions between neurons and non-neuronal cells in the human cortex.