Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. An integrative model of cellular states, plasticity, and genetics for glioblastoma. The somatic genomic landscape of glioblastoma. Source data are provided with this paper.īrennan, C. Previously published scRNA-seq data that were re-analyzed in this study are available from the following sources: Wang et al. Original CSV files for Supplementary Tables 2– 9 are available in the Supplementary Information. All other data supporting the findings of this study are available from the corresponding author on reasonable request.
Processed sc and snRNA-seq data are publicly available through the Broad Institute Single-Cell Portal ( ) and CReSCENT 60 ( study ID CRES-P23).
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We propose that glioblastomas grow out of a fundamental GSC-based neural wound response transcriptional program, which is a promising target for new therapy development.īulk RNA-seq ( EGAS00001003070 and EGAS00001004395), WGS ( EGAS00001004395), sc and snRNA-seq ( EGAS00001004656) datasets generated and analyzed in this study are available through the European Genome-Phenome Archive repository in the form of FASTQ or BAM files. Further single-cell RNA sequencing of >56,000 malignant cells from primary tumors found that the majority organize along an orthogonal astrocyte maturation gradient yet retain expression of founder GSC transcriptional programs. Genome-wide CRISPR–Cas9 dropout screens independently recapitulated this observation, with each state characterized by unique essential genes. Instead, we found that GSCs mapped along a transcriptional gradient spanning two cellular states reminiscent of normal neural development and inflammatory wound response. We observed a high degree of inter- and intra-GSC transcriptional heterogeneity that could not be fully explained by DNA somatic alterations.
To characterize functional diversity within this population, we performed single-cell RNA sequencing on >69,000 GSCs cultured from the tumors of 26 patients. Glioblastomas harbor diverse cell populations, including rare glioblastoma stem cells (GSCs) that drive tumorigenesis. Nature Cancer volume 2, pages 157–173 ( 2021) Cite this article The contextual menu now has an option to switch.Gradient of Developmental and Injury Response transcriptional states defines functional vulnerabilities underpinning glioblastoma heterogeneity
MD2withRSA) Windows: Fix launching Charles by opening a file SSL empty requests regression from 3.6.4 fixed SSL now records the correct remote address details SSL errors now more consistently displayed in the browser Authentication header viewer can now recover from slightly oddly formatted headers Closed connections regression from 3.6.4 fixedOther changes: Double-clicking a request no longer switches Structure and Sequence view. Java 1.7 bad certificate error workaround for sites that use now disabled algorithms (ie. Corrects slow startup and hung responses bugs. The contextual menu now has an option to switch.
#CHARLES PROXY 3.10.1 FOR MAC#
Finally, Charles is useful for XML development in web browsers, such as AJAX (Asynchronous Javascript and XML) and XMLHTTP.Ĭharles Web Debugging Tool for Mac is a useful tool for any developer that needs to view HTTP proxies on their Mac. For this reason, Charles for Mac is especially useful for Macromedia Flash developers as it makes it possible to view the contents of LoadVariables, LoadMovie, XML loads etc.
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