期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 293, 期 22, 页码 8315-8329出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA118.002297
关键词
mammary gland; development; breast cancer; biomarker; cell differentiation; stem cells; CDH5+cell; mammary stem cells (MaSCs); single cell RNA-seq
资金
- University of Macau, Macau SAR, China [CPG 2017-00016-FHS, SRG 2017-00045-FHS]
- Macao Science and Technology Development Fund [065/2015/A2, 094/2015/A3]
- National Natural Science Foundation of China [81602587]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据