Cell Reports (Nov 2023)
Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing
- Amanda J. Craig,
- Maruhen A. Datsch Silveira,
- Lichun Ma,
- Mahler Revsine,
- Limin Wang,
- Sophia Heinrich,
- Zachary Rae,
- Allison Ruchinskas,
- Kimia Dadkhah,
- Whitney Do,
- Shay Behrens,
- Farid R. Mehrabadi,
- Dana A. Dominguez,
- Marshonna Forgues,
- Anuradha Budhu,
- Jittiporn Chaisaingmongkol,
- Jonathan M. Hernandez,
- Jeremy L. Davis,
- Bao Tran,
- Jens U. Marquardt,
- Mathuros Ruchirawat,
- Michael Kelly,
- Tim F. Greten,
- Xin W. Wang
Affiliations
- Amanda J. Craig
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Maruhen A. Datsch Silveira
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Lichun Ma
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Mahler Revsine
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Limin Wang
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Sophia Heinrich
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hanover Medical School, 30159 Hanover, Germany
- Zachary Rae
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA
- Allison Ruchinskas
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA
- Kimia Dadkhah
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA
- Whitney Do
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Shay Behrens
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Farid R. Mehrabadi
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Dana A. Dominguez
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA
- Marshonna Forgues
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Anuradha Budhu
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Jittiporn Chaisaingmongkol
- Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Higher Education, Science, Research and Innovation, Bangkok 10400, Thailand
- Jonathan M. Hernandez
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Jeremy L. Davis
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Bao Tran
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA
- Jens U. Marquardt
- Department of Medicine I, University of Lübeck, 23552 Lübeck, Germany
- Mathuros Ruchirawat
- Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Higher Education, Science, Research and Innovation, Bangkok 10400, Thailand
- Michael Kelly
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA
- Tim F. Greten
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Xin W. Wang
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 11
p. 113446
Abstract
Summary: Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.
