Single-Cell Exome Sequencing and Monoclonal Evolution of a JAK2-Negative Myeloproliferative Neoplasm
Open accessAbstract
Tumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. Here, we describe a method for analyzing the cancer genome at a single-cell nucleotide level. To perform our analyses, we first devised and validated a high-throughput whole-genome single-cell sequencing method using two lymphoblastoid cell line single cells. We then carried out whole-exome single-cell sequencing of 90 cells from a JAK2-negative myeloproliferative neoplasm patient. The sequencing data from 58 cells passed our quality control criteria, and these data indicated that this neoplasm represented a monoclonal evolution. We further identified essential thrombocythemia (ET)-related candidate mutations such as SESN2 and NTRK1, which may be involved in neoplasm progression. This pilot study allowed the initial characterization of the disease-related genetic architecture at the single-cell nucleotide level. Further, we established a single-cell sequencing method that opens the way for detailed analyses of a variety of tumor types, including those with high genetic complex between patients.
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Rapid technological advances have enabled genome-wide profiling of RNA, DNA, protein, epigenetic modifications, chromatin accessibility, and other molecular events in single cells.
“rapid technological advances have enabled genome-wide profiling of RNA7–10, DNA11–17, protein18–21, epigenetic modifications22–26, chromatin accessibility27,28, and other molecular events29 in single cells.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [14]
Single-cell sequencing has been used to evaluate the clonal evolution of tumors.
“Single-cell sequencing has already been used to evaluate the clonal evolution of tumors (Hou et al., 2012; Navin et al., 2011; Xu et al., 2012) and the spontaneous mutation of sperm cells (Lu et al., 2012; Wang et al., 2012).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Hou et al., 2012
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- Authors
- Hou, Y., Song, L., Zhu, P., Zhang, B., Tao, Y., Xu, X., Li, F., Wu, K., Liang, J., Shao, D., Wu, H., Ye, X., Ye, C., Wu, R., Jian, M., Chen, Y., Xie, W., Zhang, R., Chen, L., Liu, X., Yao, X., Zheng, H., Yu, C., Li, Q., Gong, Z., Mao, M., Yang, X., Yang, L., Li, J., Wang, W., Lu, Z., Gu, N., Laurie, G., Bolund, L., Kristiansen, K., Wang, J., Yang, H., Li, Y., Zhang, X., & Wang, J.
- Affiliations
- BGI Group (China) (CN)
- Peking University First Hospital (CN)
- Pfizer (United States) (US)
- Kunming Institute of Zoology (CN)
- State Key Laboratory of Digital Medical Engineering (CN)
- Corresponding author
- Li, Yingrui
- Zhang, Xiuqing
- Wang, Jun
- ORCID
- Hou, Yong
- Zhu, Ping
- Zhang, Bo
- Tao, Ye
- Xu, Xun
- Li, Fuqiang
- Wu, Kui
- Wu, Hanjie
- Ye, Xiaofei
- Ye, Chen
- Wu, Renhua
- Jian, Min
- Chen, Yan
- Xie, Wei
- Chen, Lei
- Liu, Xin
- Yao, Xiaotian
- Zheng, Hancheng
- Yu, Chang
- Li, Qibin
- Mao, Mao
- Yang, Xu
- Yang, Lin
- Li, Jingxiang
- Wang, Wen
- Lu, Zuhong
- Gu, Ning
- Bolund, Lars
- Kristiansen, Karsten
- Wang, Jian
- Yang, Huanming
- Li, Yingrui
- Zhang, Xiuqing
- Wang, Jun
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 148
- Issue
- 5
- Pages
- 873-885
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2034629821
- Cited by
- 541
- References
- 40
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 12 · 2023: 16 · 2022: 42 · 2021: 28 · 2020: 24 · 2019: 34 · 2018: 51 · 2017: 48 · 2016: 51 · 2015: 44 · 2014: 65 · 2013: 63 · 2012: 44
- FWCI
- 22.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- single-cell whole-genome sequencing, tumor heterogeneity, clonal evolution, essential thrombocythemia, Sestrin2, NTRK1, driver gene identification, lymphoblastoid cell lines, cancer genomics
- MeSH terms
- Humans, Male, Middle Aged, Mutation, Myeloproliferative Disorders, Thrombocythemia, Essential, Genome, Human, Gene Expression Profiling, Janus Kinase 2, Single-Cell Analysis, High-Throughput Nucleotide Sequencing, Exome, Clonal Evolution
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