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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ATAC-Seq and RNA-Seq combined analysis elucidates the impact of BORIS/CTCFL on melanoma progression, mediated by chromatin accessibility and gene expression alterations
Rony Moscona,Sanne Marlijn Janssen,Mounib Elchebly,Andreas I. Papadakis,Alain Spatz,Eitan Rubin +5 more
TL;DR: Findings situate BORIS as a potential factor that can lead to an invasiveness phenotype, which drive melanoma progression towards metastatic dissemination.
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Bilallelic germline mutations in MAD1L1 induce a novel syndrome of aneuploidy with high tumor susceptibility
Carolina Villarroya-Beltri,Ana Osorio,Raúl Torres-Ruiz,David Gomez-Sanchez,Marianna Trakala,Agustin Sánchez-Belmonte,Fátima Mercadillo,Borja Pitarch,A Hernández‐Núñez,Antonio Gomez-Caturla,Daniel Rueda,José Perea,Sandra Rodriguez-Perales,Marcos Malumbres,Miguel Urioste +14 more
TL;DR: Novel germline biallelic mutations in MAD1L1, the gene encoding the Spindle Assembly Checkpoint (SAC) protein MAD1, are reported in a 36-year-old female with a dozen of neoplasias, including five malignant tumors, pointing to a new aneuploidy syndrome with systemic inflammation and unprecedented tumor susceptibility.
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Dual states of Bmi1-expressing intestinal stem cells drive epithelial development and tissue regeneration
Nicholas R. Smith,Sidharth K. Sengupta,P. Conley,Nicole R Giske,Christopher Klocke,Brett S. Walker,Noelle McPhail,John R. Swain,Yeon Jung Yoo,Ashley N. Anderson,Paige S. Davies,Nasim Sanati,Theresa N. Nguyen,Kristof A. Torkenczy,Andrew Adey,Jared M. Fischer,Melissa H. Wong +16 more
TL;DR: Re-evaluation of an under-appreciated Bmi1+ ISC population with fundamental importance in intestinal development re-establishes the importance of the dynamic interplay between discrete ISC populations that are regulated by opposing Wnt signaling pathways.
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Single-cell dissection of Merkel cell carcinoma heterogeneity unveils transcriptomic plasticity and therapeutic vulnerabilities.
Bhaba Krishna Das,Aarthi Kannan,Graham J Velasco,Nils Lambrecht,Quy H. Nguyen,Haibo Zhao,Jie Wu,Li Gao +7 more
TL;DR: In this paper , the authors dissect transcriptomic heterogeneity at single-cell resolution in a panel of patient tumors, revealing phenotypic plasticity in a subset of treatment-naive MCC.
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