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Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia
Sun, Heng1,2; Miao, Zhengqiang3; Zhang, Xin4; Chan, Un In4; Su, Sek Man4; Guo, Sen1; Wong, Chris Koon Ho3; Xu, Xiaoling4; Deng, Chu-Xia1
2018-06
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
Volume293Issue:22Pages:8315-8329
Abstract

The mammary gland is very intricately and well organized into distinct tissues, including epithelia, endothelia, adipocytes, and stromal and immune cells. Many mammary gland diseases, such as breast cancer, arise from abnormalities in the mammary epithelium, which is mainly composed of two distinct lineages, the basal and luminal cells. Because of the limitation of traditional transcriptome analysis of bulk mammary cells, the hierarchy and heterogeneity of mammary cells within these two lineages remain unclear. To this end, using single-cell RNA-Seq coupled with FACS analysis and principal component analysis, we determined gene expression profiles of mammary epithelial cells of virgin and pregnant mice. These analyses revealed a much higher heterogeneity among the mammary cells than has been previously reported and enabled cell classification into distinct subgroups according to signature gene markers present in each group. We also identified and verified a rare CDH5(+) cell subpopulation within a basal cell lineage as quiescent mammary stem cells (MaSCs). Moreover, using pseudo-temporal analysis, we reconstructed the developmental trajectory of mammary epithelia and uncovered distinct changes in gene expression and in biological functions of mammary cells along the developmental process. In conclusion, our work greatly refines the resolution of the cellular hierarchy in developing mammary tissues. The discovery of CDH5(+) cells as MaSCs in these tissues may have implications for our understanding of the initiation, development, and pathogenesis of mammary tumors.

KeywordMammary Gland Development Breast Cancer Biomarker Cell Differentiation Stem Cells cdh5+cell Mammary Stem Cells (Mascs) Single Cell Rna-seq
DOIhttp://doi.org/10.1074/jbc.RA118.002297
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000434205700001
PublisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
The Source to ArticleWOS
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Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorDeng, Chu-Xia
Affiliation1.Cancer Center, Faculty of Health Sciences, University of Macau, Macau SAR, China.
2.Zhuhai Research Institute, University of Macau, China
3.Genomics and Bioinformatics Core, Faculty of Health Sciences, University of Macau, Macau SAR, China.
4.Transgenic and Knockout Core, Faculty of Health Sciences, University of Macau, Macau SAR, China.
First Author AffilicationFaculty of Health Sciences;  University of Macau
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Sun, Heng,Miao, Zhengqiang,Zhang, Xin,et al. Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(22):8315-8329.
APA Sun, Heng.,Miao, Zhengqiang.,Zhang, Xin.,Chan, Un In.,Su, Sek Man.,...&Deng, Chu-Xia.(2018).Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia.JOURNAL OF BIOLOGICAL CHEMISTRY,293(22),8315-8329.
MLA Sun, Heng,et al."Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia".JOURNAL OF BIOLOGICAL CHEMISTRY 293.22(2018):8315-8329.
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