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193 results on '"Zhou, Minqi"'

1. An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis.

Author

Lee, Jin, Reyes, Nabora, Ravishankar, Supriya, Zhou, Minqi, Krasilnikov, Maria, Ringler, Christian, Pohan, Grace, Wilson, Chris, Ang, Kenny, Peng, Tien, Tsukui, Tatsuya, Sheppard, Dean, Arkin, Michelle, and Wolters, Paul

Subjects
Aging, Cellular senescence, Drug screens, Fibrosis, Pulmonology, Animals, Cyclin-Dependent Kinase Inhibitor p16, Mice, Humans, Fibroblasts, Cellular Senescence, Idiopathic Pulmonary Fibrosis, Senotherapeutics, Male, Lung, Female, HSP90 Heat-Shock Proteins
Abstract

The appearance of senescent cells in age-related diseases has spurred the search for compounds that can target senescent cells in tissues, termed senolytics. However, a major caveat with current senolytic screens is the use of cell lines as targets where senescence is induced in vitro, which does not necessarily reflect the identity and function of pathogenic senescent cells in vivo. Here, we developed a new pipeline leveraging a fluorescent murine reporter that allows for isolation and quantification of p16Ink4a+ cells in diseased tissues. By high-throughput screening in vitro, precision-cut lung slice (PCLS) screening ex vivo, and phenotypic screening in vivo, we identified a HSP90 inhibitor, XL888, as a potent senolytic in tissue fibrosis. XL888 treatment eliminated pathogenic p16Ink4a+ fibroblasts in a murine model of lung fibrosis and reduced fibrotic burden. Finally, XL888 preferentially targeted p16INK4a-hi human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF), and reduced p16INK4a+ fibroblasts from IPF PCLS ex vivo. This study provides proof of concept for a platform where p16INK4a+ cells are directly isolated from diseased tissues to identify compounds with in vivo and ex vivo efficacy in mice and humans, respectively, and provides a senolytic screening platform for other age-related diseases.

Published
2024

3. Dysregulated lung stroma drives emphysema exacerbation by potentiating resident lymphocytes to suppress an epithelial stem cell reservoir

Author

Wang, Chaoqun, Hyams, Ben, Allen, Nancy C, Cautivo, Kelly, Monahan, Kiara, Zhou, Minqi, Dahlgren, Madelene W, Lizama, Carlos O, Matthay, Michael, Wolters, Paul, Molofsky, Ari B, and Peng, Tien

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Immunology, Regenerative Medicine, Stem Cell Research - Nonembryonic - Human, Lung, Emphysema, Chronic Obstructive Pulmonary Disease, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Good Health and Well Being, Humans, Mice, Animals, Pulmonary Emphysema, Lymphocytes, Stem Cells, Pulmonary Disease, Chronic Obstructive, COPD, HHIP, adventitia, alveolar stem cell, emphysema, fibroblast, hedgehog, interferon gamma, respiratory viral infection, tissue-resident lymphocytes
Abstract

Aberrant tissue-immune interactions are the hallmark of diverse chronic lung diseases. Here, we sought to define these interactions in emphysema, a progressive disease characterized by infectious exacerbations and loss of alveolar epithelium. Single-cell analysis of human emphysema lungs revealed the expansion of tissue-resident lymphocytes (TRLs). Murine studies identified a stromal niche for TRLs that expresses Hhip, a disease-variant gene downregulated in emphysema. Stromal-specific deletion of Hhip induced the topographic expansion of TRLs in the lung that was mediated by a hyperactive hedgehog-IL-7 axis. 3D immune-stem cell organoids and animal models of viral exacerbations demonstrated that expanded TRLs suppressed alveolar stem cell growth through interferon gamma (IFNγ). Finally, we uncovered an IFNγ-sensitive subset of human alveolar stem cells that was preferentially lost in emphysema. Thus, we delineate a stromal-lymphocyte-epithelial stem cell axis in the lung that is modified by a disease-variant gene and confers host susceptibility to emphysema.

Published
2023

4. Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung

Author

Reyes, Nabora S, Krasilnikov, Maria, Allen, Nancy C, Lee, Jin Young, Hyams, Ben, Zhou, Minqi, Ravishankar, Supriya, Cassandras, Monica, Wang, Chaoqun, Khan, Imran, Matatia, Peri, Johmura, Yoshikazu, Molofsky, Ari, Matthay, Michael, Nakanishi, Makoto, Sheppard, Dean, Campisi, Judith, and Peng, Tien

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Regenerative Medicine, Stem Cell Research, Underpinning research, 1.1 Normal biological development and functioning, Humans, Basement Membrane, Biomarkers, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Fibroblasts, Inflammation, Lung, Genes, Reporter, Regeneration, Epithelial Cells, Stem Cell Niche, General Science & Technology
Abstract

We engineered an ultrasensitive reporter of p16INK4a, a biomarker of cellular senescence. Our reporter detected p16INK4a-expressing fibroblasts with certain senescent characteristics that appeared shortly after birth in the basement membrane adjacent to epithelial stem cells in the lung. Furthermore, these p16INK4a+ fibroblasts had enhanced capacity to sense tissue inflammation and respond through their increased secretory capacity to promote epithelial regeneration. In addition, p16INK4a expression was required in fibroblasts to enhance epithelial regeneration. This study highlights a role for p16INK4a+ fibroblasts as tissue-resident sentinels in the stem cell niche that monitor barrier integrity and rapidly respond to inflammation to promote tissue regeneration.

Published
2022

6. Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells

Author

Kathiriya, Jaymin J, Wang, Chaoqun, Zhou, Minqi, Brumwell, Alexis, Cassandras, Monica, Le Saux, Claude Jourdan, Cohen, Max, Alysandratos, Kostantinos-Dionysios, Wang, Bruce, Wolters, Paul, Matthay, Michael, Kotton, Darrell N, Chapman, Harold A, and Peng, Tien

Subjects
Biochemistry and Cell Biology, Biological Sciences, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Autoimmune Disease, Lung, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Alveolar Epithelial Cells, Animals, Bone Morphogenetic Proteins, Cell Differentiation, Cell Transdifferentiation, Cells, Cultured, Epidermal Cells, Epithelial Cells, Fibroblasts, Humans, Idiopathic Pulmonary Fibrosis, Keratin-5, Mesoderm, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Pulmonary Alveoli, Respiratory Mucosa, Signal Transduction, Single-Cell Analysis, Transforming Growth Factor beta1, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

Loss of alveolar type 2 cells (AEC2s) and the ectopic appearance of basal cells in the alveoli characterize severe lung injuries such as idiopathic pulmonary fibrosis (IPF). Here we demonstrate that human alveolar type 2 cells (hAEC2s), unlike murine AEC2s, transdifferentiate into basal cells in response to fibrotic signalling in the lung mesenchyme, in vitro and in vivo. Single-cell analysis of normal hAEC2s and mesenchymal cells in organoid co-cultures revealed the emergence of pathologic fibroblasts and basaloid cells previously described in IPF. Transforming growth factor-β1 and anti-bone morphogenic protein signalling in the organoids promoted transdifferentiation. Trajectory and histologic analyses of both hAEC2-derived organoids and IPF epithelium indicated that hAEC2s transdifferentiate into basal cells through alveolar-basal intermediates that accumulate in proximity to pathologic CTHRC1hi/TGFB1hi fibroblasts. Our study indicates that hAEC2 loss and expansion of alveolar metaplastic basal cells in severe human lung injuries are causally connected through an hAEC2-basal cell lineage trajectory driven by aberrant mesenchyme.

Published
2022

7. Automatic View Selection in Graph Databases

Author

Zhang, Chao, Lu, Jiaheng, Guo, Qingsong, Zhang, Xinyong, Han, Xiaochun, and Zhou, Minqi

Subjects
Computer Science - Databases
Abstract

Recently, several works have studied the problem of view selection in graph databases. However, existing methods cannot fully exploit the graph properties of views, e.g., supergraph views and common subgraph views, which leads to a low view utility and duplicate view content. To address the problem, we propose an end-to-end graph view selection tool, G-View, which can judiciously generate a view set from a query workload by exploring the graph properties of candidate views and considering their efficacy. Specifically, given a graph query set and a space budget, G-View translates each query to a candidate view pattern and checks the query containment via a filtering-and-verification framework. G-View then selects the views using a graph gene algorithm (GGA), which relies on a three-phase framework that explores graph view transformations to reduce the view space and optimize the view benefit. Finally, G-View generates the extended graph views that persist all the edge-induced subgraphs to answer the subgraph and supergraph queries simultaneously. Extensive experiments on real-life and synthetic datasets demonstrated G-View achieved averagely 21x and 2x query performance speedup over two view-based methods while having 2x and 5x smaller space overhead, respectively. Moreover, the proposed selection algorithm, GGA, outperformed other selection methods in both effectiveness and efficiency.

Published
2021

20. Low Overhead Log Replication for Main Memory Database System

Author

Guo, Jinwei, Zhang, Chendong, Cai, Peng, Zhou, Minqi, Zhou, Aoying, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Cui, Bin, editor, Zhang, Nan, editor, Xu, Jianliang, editor, Lian, Xiang, editor, and Liu, Dexi, editor

Published
2016
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21. Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+basal cells

Author

Kathiriya, Jaymin J., Wang, Chaoqun, Zhou, Minqi, Brumwell, Alexis, Cassandras, Monica, Le Saux, Claude Jourdan, Cohen, Max, Alysandratos, Kostantinos-Dionysios, Wang, Bruce, Wolters, Paul, Matthay, Michael, Kotton, Darrell N., Chapman, Harold A., and Peng, Tien

Abstract

Loss of alveolar type 2 cells (AEC2s) and the ectopic appearance of basal cells in the alveoli characterize severe lung injuries such as idiopathic pulmonary fibrosis (IPF). Here we demonstrate that human alveolar type 2 cells (hAEC2s), unlike murine AEC2s, transdifferentiate into basal cells in response to fibrotic signalling in the lung mesenchyme, in vitro and in vivo. Single-cell analysis of normal hAEC2s and mesenchymal cells in organoid co-cultures revealed the emergence of pathologic fibroblasts and basaloid cells previously described in IPF. Transforming growth factor-β1 and anti-bone morphogenic protein signalling in the organoids promoted transdifferentiation. Trajectory and histologic analyses of both hAEC2-derived organoids and IPF epithelium indicated that hAEC2s transdifferentiate into basal cells through alveolar-basal intermediates that accumulate in proximity to pathologic CTHRC1hi/TGFB1hifibroblasts. Our study indicates that hAEC2 loss and expansion of alveolar metaplastic basal cells in severe human lung injuries are causally connected through an hAEC2-basal cell lineage trajectory driven by aberrant mesenchyme.

Published
2024
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22. A Scalable Framework for Universal Data Generation in Parallel

Author

Gu, Ling, Zhou, Minqi, Kang, Qiangqiang, Zhou, Aoying, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Nambiar, Raghunath, editor, and Poess, Meikel, editor

Published
2015
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25. BSMA-Gen: A Parallel Synthetic Data Generator for Social Media Timeline Structures

Author

Yu, Chengcheng, Xia, Fan, Zhang, Qunyan, Ma, Haixin, Qian, Weining, Zhou, Minqi, Jin, Cheqing, Zhou, Aoying, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Bhowmick, Sourav S., editor, Dyreson, Curtis E., editor, Jensen, Christian S., editor, Lee, Mong Li, editor, Muliantara, Agus, editor, and Thalheim, Bernhard, editor

Published
2014
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27. Sentinel p16 INK4a+ cells in the basement membrane form a reparative niche in the lung

Author

Reyes, Nabora S., primary, Krasilnikov, Maria, additional, Allen, Nancy C., additional, Lee, Jin Young, additional, Hyams, Ben, additional, Zhou, Minqi, additional, Ravishankar, Supriya, additional, Cassandras, Monica, additional, Wang, Chaoqun, additional, Khan, Imran, additional, Matatia, Peri, additional, Johmura, Yoshikazu, additional, Molofsky, Ari, additional, Matthay, Michael, additional, Nakanishi, Makoto, additional, Sheppard, Dean, additional, Campisi, Judith, additional, and Peng, Tien, additional

Published
2022
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29. Adaptive Query Scheduling in Key-Value Data Stores

Author

Xu, Chen, Sharaf, Mohamed A., Zhou, Minqi, Zhou, Aoying, Zhou, Xiaofang, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Meng, Weiyi, editor, Feng, Ling, editor, Bressan, Stéphane, editor, Winiwarter, Werner, editor, and Song, Wei, editor

Published
2013
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30. Detecting User Preference on Microblog

Author

Xu, Chen, Zhou, Minqi, Chen, Feng, Zhou, Aoying, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Meng, Weiyi, editor, Feng, Ling, editor, Bressan, Stéphane, editor, Winiwarter, Werner, editor, and Song, Wei, editor

Published
2013
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31. An SVM-Based Approach to Discover MicroRNA Precursors in Plant Genomes

Author

Wang, Yi, Jin, Cheqing, Zhou, Minqi, Zhou, Aoying, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Goebel, Randy, editor, Siekmann, Jörg, editor, Wahlster, Wolfgang, editor, Cao, Longbing, editor, Huang, Joshua Zhexue, editor, Bailey, James, editor, Koh, Yun Sing, editor, and Luo, Jun, editor

Published
2012
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32. At the Frontiers of Information and Software as Services

Author

Candan, K. Selçuk, Li, Wen-Syan, Phan, Thomas, Zhou, Minqi, van der Aalst, Will, Series editor, Mylopoulos, John, Series editor, Sadeh, Norman M., Series editor, Shaw, Michael J., Series editor, Szyperski, Clemens, Series editor, Agrawal, Divyakant, editor, Candan, K. Selçuk, editor, and Li, Wen-Syan, editor

Published
2011
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34. A Fast Video Stabilization System Based on Speeded-up Robust Features

Author

Zhou, Minqi, Asari, Vijayan K., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Bebis, George, editor, Boyle, Richard, editor, Parvin, Bahram, editor, Koracin, Darko, editor, Wang, Song, editor, Kyungnam, Kim, editor, Benes, Bedrich, editor, Moreland, Kenneth, editor, Borst, Christoph, editor, DiVerdi, Stephen, editor, Yi-Jen, Chiang, editor, and Ming, Jiang, editor

Published
2011
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35. Optimized Data Placement for Column-Oriented Data Store in the Distributed Environment

Author

Zhou, Minqi, Xu, Chen, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Xu, Jianliang, editor, Yu, Ge, editor, Zhou, Shuigeng, editor, and Unland, Rainer, editor

Published
2011
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36. AUCWeb: A Prototype for Analyzing User-Created Web Data

Author

Qian, Weining, Chen, Feng, Du, Juan, Zhang, Weiming, Zhang, Can, Ma, Haixin, Cai, Peng, Zhou, Minqi, Zhou, Aoying, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Yu, Jeffrey Xu, editor, Kim, Myoung Ho, editor, and Unland, Rainer, editor

Published
2011
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37. GChord: Indexing for Multi-Attribute Query in P2P System with Low Maintenance Cost

Author

Zhou, Minqi, Zhang, Rong, Qian, Weining, Zhou, Aoying, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Kotagiri, Ramamohanarao, editor, Krishna, P. Radha, editor, Mohania, Mukesh, editor, and Nantajeewarawat, Ekawit, editor

Published
2007
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43. Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells

Author

Kathiriya, Jaymin J., primary, Wang, Chaoqun, additional, Zhou, Minqi, additional, Brumwell, Alexis, additional, Cassandras, Monica, additional, Le Saux, Claude Jourdan, additional, Cohen, Max, additional, Alysandratos, Kostantinos-Dionysios, additional, Wang, Bruce, additional, Wolters, Paul, additional, Matthay, Michael, additional, Kotton, Darrell N., additional, Chapman, Harold A., additional, and Peng, Tien, additional

Published
2021
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