Department of Cancer Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Integrative Genomics Core, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Commun Biol. 2021 Jun 2;4(1):660. doi: 10.1038/s42003-021-02201-2.
The female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K human mammary epithelial cell atlases obtained by single-cell RNA sequencing, which covers most lifetime stages. Our results indicate a putative trajectory that originates from embryonic mammary stem cells which differentiates into three epithelial lineages (basal, luminal hormone-sensing, and luminal alveolar), presumably arising from unipotent progenitors in postnatal glands. The lineage-specific genes infer cells of origin of breast cancer using The Cancer Genome Atlas data and single-cell RNA sequencing of human breast cancer, as well as the association of gland reorganization to different breast cancer subtypes. This comprehensive mammary cell gene expression atlas ( https://mouse-mammary-epithelium-integrated.cells.ucsc.edu ) presents insights into the impact of the internal and external stimuli on the mammary epithelium at an advanced resolution.
女性乳腺上皮组织在发育、妊娠和绝经期间会发生重组，这将使乳腺癌的发病风险更高。为了描述这些复杂重塑的时期，我们在此报告了通过单细胞 RNA 测序获得的整合了 50K 只小鼠和 24K 只人类乳腺上皮细胞图谱，这些图谱涵盖了大多数生命周期阶段。我们的研究结果表明，一个假定的轨迹起源于胚胎乳腺干细胞，其分化为三个上皮谱系（基底、腔激素感应和腔肺泡），这些谱系可能来自于出生后腺体中的单能祖细胞。通过癌症基因组图谱数据和人类乳腺癌的单细胞 RNA 测序以及腺体重组与不同乳腺癌亚型的关联，这些谱系特异性基因推断出了乳腺癌的细胞起源。这个综合的乳腺细胞基因表达图谱（https://mouse-mammary-epithelium-integrated.cells.ucsc.edu）深入了解了内部和外部刺激对乳腺上皮组织的影响。
