Browsing by Author "Xu, Chuan"

Now showing 1 - 4 of 4
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    An integrated cell atlas of the lung in health and disease.
    (Nature medicine, 2023-06) Sikkema, Lisa; Ramírez-Suástegui, Ciro; Strobl, Daniel C; Gillett, Tessa E; Zappia, Luke; Madissoon, Elo; Markov, Nikolay S; Zaragosi, Laure-Emmanuelle; Ji, Yuge; Ansari, Meshal; Arguel, Marie-Jeanne; Apperloo, Leonie; Banchero, Martin; Bécavin, Christophe; Berg, Marijn; Chichelnitskiy, Evgeny; Chung, Mei-I; Collin, Antoine; Gay, Aurore CA; Gote-Schniering, Janine; Hooshiar Kashani, Baharak; Inecik, Kemal; Jain, Manu; Kapellos, Theodore S; Kole, Tessa M; Leroy, Sylvie; Mayr, Christoph H; Oliver, Amanda J; von Papen, Michael; Peter, Lance; Taylor, Chase J; Walzthoeni, Thomas; Xu, Chuan; Bui, Linh T; De Donno, Carlo; Dony, Leander; Faiz, Alen; Guo, Minzhe; Gutierrez, Austin J; Heumos, Lukas; Huang, Ni; Ibarra, Ignacio L; Jackson, Nathan D; Kadur Lakshminarasimha Murthy, Preetish; Lotfollahi, Mohammad; Tabib, Tracy; Talavera-López, Carlos; Travaglini, Kyle J; Wilbrey-Clark, Anna; Worlock, Kaylee B; Yoshida, Masahiro; Lung Biological Network Consortium; van den Berge, Maarten; Bossé, Yohan; Desai, Tushar J; Eickelberg, Oliver; Kaminski, Naftali; Krasnow, Mark A; Lafyatis, Robert; Nikolic, Marko Z; Powell, Joseph E; Rajagopal, Jayaraj; Rojas, Mauricio; Rozenblatt-Rosen, Orit; Seibold, Max A; Sheppard, Dean; Shepherd, Douglas P; Sin, Don D; Timens, Wim; Tsankov, Alexander M; Whitsett, Jeffrey; Xu, Yan; Banovich, Nicholas E; Barbry, Pascal; Duong, Thu Elizabeth; Falk, Christine S; Meyer, Kerstin B; Kropski, Jonathan A; Pe'er, Dana; Schiller, Herbert B; Tata, Purushothama Rao; Schultze, Joachim L; Teichmann, Sara A; Misharin, Alexander V; Nawijn, Martijn C; Luecken, Malte D; Theis, Fabian J
    Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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    Inositol serves as a natural inhibitor of mitochondrial fission by directly targeting AMPK.
    (Molecular cell, 2021-09) Hsu, Che-Chia; Zhang, Xian; Wang, Guihua; Zhang, Weina; Cai, Zhen; Pan, Bo-Syong; Gu, Haiwei; Xu, Chuan; Jin, Guoxiang; Xu, Xiangshang; Manne, Rajesh Kumar; Jin, Yan; Yan, Wei; Shao, Jingwei; Chen, Tingjin; Lin, Emily; Ketkar, Amit; Eoff, Robert; Xu, Zhi-Gang; Chen, Zhong-Zhu; Li, Hong-Yu; Lin, Hui-Kuan
    Mitochondrial dynamics regulated by mitochondrial fusion and fission maintain mitochondrial functions, whose alterations underline various human diseases. Here, we show that inositol is a critical metabolite directly restricting AMPK-dependent mitochondrial fission independently of its classical mode as a precursor for phosphoinositide generation. Inositol decline by IMPA1/2 deficiency elicits AMPK activation and mitochondrial fission without affecting ATP level, whereas inositol accumulation prevents AMPK-dependent mitochondrial fission. Metabolic stress or mitochondrial damage causes inositol decline in cells and mice to elicit AMPK-dependent mitochondrial fission. Inositol directly binds to AMPKγ and competes with AMP for AMPKγ binding, leading to restriction of AMPK activation and mitochondrial fission. Our study suggests that the AMP/inositol ratio is a critical determinant for AMPK activation and establishes a model in which AMPK activation requires inositol decline to release AMPKγ for AMP binding. Hence, AMPK is an inositol sensor, whose inactivation by inositol serves as a mechanism to restrict mitochondrial fission.
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    Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS
    (Cell, 2019-06) Zhang, Weina; Wang, Guihua; Xu, Zhi-Gang; Tu, Haiqing; Hu, Fuqing; Dai, Jiang; Chang, Yan; Chen, Yaqi; Lu, Yanjun; Zeng, Haolong; Cai, Zhen; Han, Fei; Xu, Chuan; Jin, Guoxiang; Sun, Li; Pan, Bo-Syong; Lai, Shiue-Wei; Hsu, Che-Chia; Xu, Jia; Chen, Zhong-Zhu; Li, Hong-Yu; Seth, Pankaj; Hu, Junbo; Zhang, Xuemin; Li, Huiyan; Lin, Hui-Kuan
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    SIRPγ-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling.
    (The Journal of clinical investigation, 2022-03) Xu, Chuan; Jin, Guoxiang; Wu, Hong; Cui, Wei; Wang, Yu-Hui; Manne, Rajesh Kumar; Wang, Guihua; Zhang, Weina; Zhang, Xian; Han, Fei; Cai, Zhen; Pan, Bo-Syong; Hsu, Che-Chia; Liu, Yiqiang; Zhang, Anmei; Long, Jie; Zou, Hongbo; Wang, Shuang; Ma, Xiaodan; Duan, Jinling; Wang, Bin; Liu, Weihui; Lan, Haitao; Xiong, Qing; Xue, Gang; Chen, Zhongzhu; Xu, Zhigang; Furth, Mark E; Haigh Molina, Sarah; Lu, Yong; Xie, Dan; Bian, Xiu-Wu; Lin, Hui-Kuan
    Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγhi and SIRPγlo/- tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγhi cells serve as CSLCs and tumor immune checkpoint-initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.