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Regner MJ, Wisniewska K, Garcia-Recio S, et al. A multi-omic single-cell landscape of human gynecologic malignancies. Mol Cell. 2021;81(23):4924-4941.e10doi: 10.1016/j.molcel.2021.10.013.
Regner, M. J., Wisniewska, K., Garcia-Recio, S., Thennavan, A., Mendez-Giraldez, R., Malladi, V. S., Hawkins, G., Parker, J. S., Perou, C. M., Bae-Jump, V. L., & Franco, H. L. (2021). A multi-omic single-cell landscape of human gynecologic malignancies. Molecular cell, 81(23), 4924-4941.e10. https://doi.org/10.1016/j.molcel.2021.10.013
Regner, Matthew J, et al. "A multi-omic single-cell landscape of human gynecologic malignancies." Molecular cell vol. 81,23 (2021): 4924-4941.e10. doi: https://doi.org/10.1016/j.molcel.2021.10.013
Regner MJ, Wisniewska K, Garcia-Recio S, Thennavan A, Mendez-Giraldez R, Malladi VS, Hawkins G, Parker JS, Perou CM, Bae-Jump VL, Franco HL. A multi-omic single-cell landscape of human gynecologic malignancies. Mol Cell. 2021 Dec 02;81(23):4924-4941.e10. doi: 10.1016/j.molcel.2021.10.013. Epub 2021 Nov 04. PMID: 34739872; PMCID: PMC8642316.
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Mol Cell. 2021 Dec 02;81(23):4924-4941.e10. doi: 10.1016/j.molcel.2021.10.013. Epub 2021 Nov 04.

A multi-omic single-cell landscape of human gynecologic malignancies.

Molecular cell

Matthew J Regner, Kamila Wisniewska, Susana Garcia-Recio, Aatish Thennavan, Raul Mendez-Giraldez, Venkat S Malladi, Gabrielle Hawkins, Joel S Parker, Charles M Perou, Victoria L Bae-Jump, Hector L Franco

Affiliations

  1. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Bioinformatics and Computational Biology Graduate Program, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  2. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Oral and Craniofacial Biomedicine Program, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  4. Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  5. Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  6. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  7. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  8. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  9. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Bioinformatics and Computational Biology Graduate Program, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: [email protected].

PMID: 34739872 PMCID: PMC8642316 DOI: 10.1016/j.molcel.2021.10.013

Abstract

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.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: chromatin accessibility; endometrial cancer; enhancer elements; gastro-intestinal stromal tumors; gene regulation; intratumoral heterogeneity; ovarian cancer; scATAC-seq; scRNA-seq; single-cell genomics

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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