Open Access
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Itay Tirosh,Benjamin Izar,Daniel J. Treacy,John J. Trombetta,Asaf Rotem,Christopher Rodman,Christine G. Lian,George F. Murphy,Mohammad Fallahi-Sichani,Ken Dutton-Regester,Jia-Ren Lin,Ofir Cohen,Parin Shah,Diana Lu,Alexandra-Chloé Villani,Aleksandr Andreev,E.M. Van Allen,Monica M. Bertagnolli,Peter K. Sorger,Ryan J. Sullivan,Keith T. Flaherty,Dennie T. Frederick,Judit Jané-Valbuena,Orit Rozenblatt-Rosen,Sanjay M. Prakadan,Marc H. Wadsworth,Alex S. Genshaft,Travis K. Hughes,Carly G. K. Ziegler,Samuel W. Kazer,Alethe Gaillard de Saint Germain,Kellie E. Kolb,Cory M. Johannessen,Clifford H. Yoon,Alex K. Shalek,Aviv Regev,Levi A. Garraway +36 more
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TLDR
Tirosh et al. as discussed by the authors applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells.Abstract:
Single-cell expression profiles of melanoma Tumors harbor multiple cell types that are thought to play a role in the development of resistance to drug treatments. Tirosh et al. used single-cell sequencing to investigate the distribution of these differing genetic profiles within melanomas. Many cells harbored heterogeneous genetic programs that reflected two different states of genetic expression, one of which was linked to resistance development. Following drug treatment, the resistance-linked expression state was found at a much higher level. Furthermore, the environment of the melanoma cells affected their gene expression programs. Science, this issue p. 189 Melanoma cells show transcriptional heterogeneity. To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.read more
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Direct chemical reprogramming of human cord blood erythroblasts to induced megakaryocytes that produce platelets.
Jinhua Qin,Jian Zhang,Jianan Jiang,Bowen Zhang,Jisheng Li,Xiaosong Lin,Sihan Wang,Meiqi Zhu,Zeng Fan,Yang Lv,Lijuan He,Lin Chen,Wen Yue,Yanhua Li,Xuetao Pei +14 more
TL;DR: In this paper , a combination of four small molecules (4M) successfully converted human cord blood erythroblasts (EBs) into induced megakaryocytes (iMKs).
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Stepwise activities of mSWI/SNF family chromatin remodeling complexes direct T cell activation and exhaustion
Elena Battistello,Kimberlee A. Hixon,Dawn E. Comstock,Clayton K. Collings,Xufeng Chen,Javier Rodríguez Hernáez,Soobeom Lee,Kasey Cervantes,Madeline M. Hinkley,Konstantinos Ntatsoulis,Annamaria Cesarano,Kathryn Hockemeyer,W. Nicholas Haining,Matthew T. Witkowski,J Qi,Aristotelis Tsirigos,Fabiana Perna,Iannis Aifantis,Cigall Kadoch +18 more
TL;DR: In this article , the authors comprehensively profile the genomic occupancy of mSWI/SNF chromatin remodeling complexes throughout acute and chronic T cell stimulation, finding that stepwise changes in localization over transcription factor binding sites direct site-specific chromatin accessibility and gene activation leading to distinct phenotypes.
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Relationship Between CNVs and Immune Cells Infiltration in Gastric Tumor Microenvironment
Fazhan Li,Huijuan Wen,Ihtisham Bukhari,Bin Liu,Chenxu Guo,Feifei Ren,Youcai Tang,Yang Mi,Peng-Yuan Zheng +8 more
TL;DR: It is concluded that CNVs are key regulators of the immune cells infiltration in gastric TME as well as cancer development, and CPVL could potentially be used as a prognostic and therapeutic marker in Gastric cancer.
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Differential expression of CCR8 in tumors versus normal tissue allows specific depletion of tumor-infiltrating T regulatory cells by GS-1811, a novel Fc-optimized anti-CCR8 antibody
Jessica D. Weaver,Edward C. Stack,Joshua A. Buggé,Changyun Hu,Lara McGrath,Amy Mueller,Masie Wong,Boris Klebanov,T Mujeeb Rahman,Rosemary Kaufman,Christine Fregeau,Vikki Spaulding,M Priess,Kristin Legendre,Sarah Jaffe,Dhruvkumar Upadhyay,Anjala Singh,Changgang Xu,Kristin Krukenberg,Yan Zhang,Yassine Ezzyat,Dorothée Saddier Axe,Michelle Kuhne,Michael Meehl,Donald R. Shaffer,Brian M. Weist,Dmitri Wiederschain,Fabien Dépis,Monica Gostissa +28 more
TL;DR: GS-1811 as discussed by the authors is a novel therapeutic monoclonal antibody that specifically binds to human CCR8 and is designed to selectively deplete tumor-infiltrating Tregs.
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The integration of single-cell sequencing, TCGA, and GEO data analysis revealed that PRRT3-AS1 is a biomarker and therapeutic target of SKCM
Wancong Zhang,Xuqi Xie,Zijian Huang,Xiaoping Zhong,Yang Li,Kit-Leong Cheong,Jianda Zhou,Shijie Tang +7 more
TL;DR: PRRT3-AS1 may be a diagnostic and prognostic biomarker of SKCM and was found to be related to epithelial-mesenchymal transition (EMT) signaling pathways and suppress immune infiltration and be involved in immunotherapy resistance.
References
More filters
Journal ArticleDOI
Hallmarks of cancer: the next generation.
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI
Fast and accurate short read alignment with Burrows–Wheeler transform
Heng Li,Richard Durbin +1 more
TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Journal Article
Visualizing Data using t-SNE
TL;DR: A new technique called t-SNE that visualizes high-dimensional data by giving each datapoint a location in a two or three-dimensional map, a variation of Stochastic Neighbor Embedding that is much easier to optimize, and produces significantly better visualizations by reducing the tendency to crowd points together in the center of the map.
Journal ArticleDOI
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)
Elizabeth Eisenhauer,P. Therasse,Jan Bogaerts,Lawrence H. Schwartz,Daniel J. Sargent,Robert Ford,Janet Dancey,S. Arbuck,S. Gwyther,Margaret M. Mooney,Larry Rubinstein,Lalitha K. Shankar,Lori E. Dodd,Robert M. Kaplan,Denis Lacombe,Jaap Verweij +15 more
TL;DR: The revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions, and a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included.
Journal ArticleDOI
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
Aaron McKenna,Matthew Hanna,Eric Banks,Andrey Sivachenko,Kristian Cibulskis,Andrew Kernytsky,Kiran V. Garimella,David Altshuler,Stacey Gabriel,Mark J. Daly,Mark A. DePristo +10 more
TL;DR: The GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.
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