College of Biological and Food Engineering, Jilin Engineering Normal University, Changchun, China.
Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
PLoS One. 2022 Apr 29;17(4):e0267211. doi: 10.1371/journal.pone.0267211. eCollection 2022.
Mammary gland is present in all mammals and usually functions in producing milk to feed the young offspring. Mammogenesis refers to the growth and development of mammary gland, which begins at puberty and ends after lactation. Pregnancy is regulated by various cytokines, which further contributes to mammary gland development. Epithelial cells, including basal and luminal cells, are one of the major components of mammary gland cells. The development of basal and luminal cells has been observed to significantly differ at different stages. However, the underlying mechanisms for differences between basal and luminal cells have not been fully studied. To explore the mechanisms underlying the differentiation of mammary progenitors or their offspring into luminal and myoepithelial cells, the single-cell sequencing data on mammary epithelia cells of virgin and pregnant mouse was deeply investigated in this work. We evaluated features by using Monte Carlo feature selection and plotted the incremental feature selection curve with support vector machine or RIPPER to find the optimal gene features and rules that can divide epithelial cells into four clusters with different cell subtypes like basal and luminal cells and different phases like pregnancy and virginity. As representations, the feature genes Cldn7, Gjb6, Sparc, Cldn3, Cited1, Krt17, Spp1, Cldn4, Gjb2 and Cldn19 might play an important role in classifying the epithelial mammary cells. Notably, seven most important rules based on the combination of cell-specific and tissue-specific expressions of feature genes effectively classify the epithelial mammary cells in a quantitative and interpretable manner.
乳腺存在于所有哺乳动物中，通常负责分泌乳汁来喂养幼崽。乳腺发生是指乳腺的生长和发育，始于青春期，结束于哺乳期。妊娠受多种细胞因子的调节，这些细胞因子进一步促进乳腺发育。上皮细胞包括基底细胞和腔细胞，是乳腺细胞的主要成分之一。在不同阶段，基底细胞和腔细胞的发育明显不同。然而，基底细胞和腔细胞之间差异的潜在机制尚未得到充分研究。为了探索乳腺祖细胞或其后代分化为腔细胞和肌上皮细胞的机制，本研究深入研究了处女和妊娠小鼠乳腺上皮细胞的单细胞测序数据。我们通过蒙特卡罗特征选择来评估特征，并使用支持向量机或 RIPPER 绘制增量特征选择曲线，以找到最佳的基因特征和规则，这些特征和规则可以将上皮细胞分为四个具有不同细胞亚型（如基底细胞和腔细胞）和不同阶段（如妊娠和处女）的簇。作为代表，特征基因 Cldn7、Gjb6、Sparc、Cldn3、Cited1、Krt17、Spp1、Cldn4、Gjb2 和 Cldn19 可能在将上皮乳腺细胞分类中发挥重要作用。值得注意的是，基于特征基因的细胞特异性和组织特异性表达的七个最重要的规则，可以有效地以定量和可解释的方式对上皮乳腺细胞进行分类。
