Single-cell transcriptomics reveal the heterogeneity and dynamic of cancer stem-like cells during breast tumor progression. 2021

Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; The Shanghai Key Laboratory of Medical Epigenetics; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College; Fudan University, 200032, Shanghai, China.

Breast cancer stem-like cells (BCSCs) play vital roles in tumorigenesis and progression. However, the origin and dynamic changes of BCSCs are still to be elucidated. Using the breast cancer mouse model MMTV-PyMT, we constructed a single-cell atlas of 31,778 cells from four distinct stages of tumor progression (hyperplasia, adenoma/MIN, early carcinoma and late carcinoma), during which malignant transition occurs. We identified that the precise cell type of ERlow epithelial cell lineage gave rise to the tumors, and the differentiation of ERhigh epithelial cell lineage was blocked. Furthermore, we discovered a specific signature with a continuum of gene expression profiles along the tumor progression and significantly correlated with clinical outcomes, and we also found a stem-like cell cluster existed among ERlow epithelial cells. Further clustering on this stem-like cluster showed several sub-clusters indicating heterogeneity of stem-like epithelial cells. Moreover, we distinguished normal and cancer stem-like cells in this stem-like epithelial cell cluster and profiled the molecular portraits from normal stem-like cell to cancer stem-like cells during the malignant transition. Finally, we found the diverse immune cell infiltration displayed immunosuppressive characteristics along tumor progression. We also found the specific expression pattern of cytokines and their corresponding cytokine receptors in BCSCs and immune cells, suggesting the possible cross-talk between BCSCs and the immune cells. These data provide a useful resource for illuminating BCSC heterogeneity and the immune cell remodeling during breast tumor progression, and shed new light on transcriptomic dynamics during the progression at the single-cell level.

UI MeSH Term Description Entries
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014411 Neoplastic Stem Cells Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS. Cancer Stem Cells,Colony-Forming Units, Neoplastic,Stem Cells, Neoplastic,Tumor Stem Cells,Neoplastic Colony-Forming Units,Tumor Initiating Cells,Cancer Stem Cell,Cell, Cancer Stem,Cell, Neoplastic Stem,Cell, Tumor Initiating,Cell, Tumor Stem,Cells, Cancer Stem,Cells, Neoplastic Stem,Cells, Tumor Initiating,Cells, Tumor Stem,Colony Forming Units, Neoplastic,Colony-Forming Unit, Neoplastic,Initiating Cell, Tumor,Initiating Cells, Tumor,Neoplastic Colony Forming Units,Neoplastic Colony-Forming Unit,Neoplastic Stem Cell,Stem Cell, Cancer,Stem Cell, Neoplastic,Stem Cell, Tumor,Stem Cells, Cancer,Stem Cells, Tumor,Tumor Initiating Cell,Tumor Stem Cell,Unit, Neoplastic Colony-Forming,Units, Neoplastic Colony-Forming
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D059010 Single-Cell Analysis Assaying the products of or monitoring various biochemical processes and reactions in an individual cell. Analyses, Single-Cell,Analysis, Single-Cell,Single Cell Analysis,Single-Cell Analyses
D059467 Transcriptome The pattern of GENE EXPRESSION at the level of genetic transcription in a specific organism or under specific circumstances in specific cells. Transcriptomes,Gene Expression Profiles,Gene Expression Signatures,Transcriptome Profiles,Expression Profile, Gene,Expression Profiles, Gene,Expression Signature, Gene,Expression Signatures, Gene,Gene Expression Profile,Gene Expression Signature,Profile, Gene Expression,Profile, Transcriptome,Profiles, Gene Expression,Profiles, Transcriptome,Signature, Gene Expression,Signatures, Gene Expression,Transcriptome Profile
D018450 Disease Progression The worsening and general progression of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. Clinical Course,Clinical Progression,Disease Exacerbation,Exacerbation, Disease,Progression, Clinical,Progression, Disease

Related Publications

Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
June 2023, BMC biology,
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
June 2018, Nature communications,
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
January 2023, Frontiers in cell and developmental biology,
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
February 2023, Advanced science (Weinheim, Baden-Wurttemberg, Germany),
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
August 2021, Cell stem cell,
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
May 2024, Cancer research,
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
January 2021, Analytical chemistry,
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
September 2022, Cytokine,
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
June 2015, Cell reports,
Guojuan Jiang, and Juchuanli Tu, and Lei Zhou, and Mengxue Dong, and Jue Fan, and Zhaoxia Chang, and Lixing Zhang, and Xiuwu Bian, and Suling Liu
October 2007, Cell cycle (Georgetown, Tex.),
Copied contents to your clipboard!