A multi-omic single-cell landscape of human gynecologic malignancies
| Autor: | Susana García-Recio, Charles M. Perou, Kamila Wisniewska, Victoria L. Bae-Jump, Aatish Thennavan, Venkat S. Malladi, Gabrielle Hawkins, Matthew J. Regner, Joel S. Parker, Raul Mendez-Giraldez, Hector L. Franco |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Epithelial-Mesenchymal Transition Carcinogenesis Gastrointestinal Stromal Tumors Kaplan-Meier Estimate Computational biology Biology medicine.disease_cause Article Transcriptome RNA Small Cytoplasmic medicine Humans RNA-Seq Regulatory Elements Transcriptional Molecular Biology Transcription factor Aged Gene Library Ovarian Neoplasms Regulation of gene expression Ovary Cancer Genomics Oncogenes Cell Biology Middle Aged medicine.disease Chromatin Enhancer Elements Genetic Genetic Techniques Cancer cell Female Ovarian cancer Transcription Factors |
| Zdroj: | Mol Cell |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2021.10.013 |
| Popis: | Deconvolution of regulatory mechanisms that drive transcriptional programs in cancer cells is key to understanding tumor biology. Herein, we present matched transcriptome (scRNA-seq) and chromatin accessibility (scATAC-seq) profiles at single-cell resolution from human ovarian and endometrial tumors processed immediately following surgical resection. This dataset reveals the complex cellular heterogeneity of these tumors and enabled us to quantitatively link variation in chromatin accessibility to gene expression. We show that malignant cells acquire previously unannotated regulatory elements to drive hallmark cancer pathways. Moreover, malignant cells from within the same patients show substantial variation in chromatin accessibility linked to transcriptional output, highlighting the importance of intratumoral heterogeneity. Finally, we infer the malignant cell type-specific activity of transcription factors. By defining the regulatory logic of cancer cells, this work reveals an important reliance on oncogenic regulatory elements and highlights the ability of matched scRNA-seq/scATAC-seq to uncover clinically relevant mechanisms of tumorigenesis in gynecologic cancers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|