The existence of mammary epithelial stem cell(MaSC)populations capable of mediating mammary gland development and homeostasis has been established for over a decade.A combination of lineage tracing and mammary gland t...The existence of mammary epithelial stem cell(MaSC)populations capable of mediating mammary gland development and homeostasis has been established for over a decade.A combination of lineage tracing and mammary gland transplantation studies has affirmed that MaSCs and their downstream progenitors are organized in a hierarchal manner;however,these techniques have failed to illuminate the complete spectrum of epithelial intermediate populations or their spatial and temporal relationships.The advent of single cell sequencing technology has allowed for characterization of highly heterogeneous tissues at high resolution.In the last two years,the remarkable advances in single cell RNA sequencing technologies have been leveraged to address the heterogeneity of the mammary epithelium.These studies have afforded fresh insights into the transcriptional differentiation hierarchy and its chronology.Importantly,these data have led to a major conceptual shift in which the rigid boundaries separating stem,progenitor,and differentiated epithelial populations have been deconstructed,resulting in a new more fluid and flexible model of epithelial differentiation.The emerging view of the mammary epithelial hierarchy has important implications for mammary development,carcinogenesis,and metastasis,providing novel insights into the underlying cellular states that may promote malignant phenotypes.展开更多
旨在探究奶牛乳腺上皮细胞(BMECs)与脐带间充质干细胞(UC-MSCs)共培养对(BMECs)乳脂合成及关键基因表达的影响。试验共分为8组:共培养组为UC-MSCs和BMECs共培养条件下的不处理组、IGF-1R抑制剂AG1024处理组、Janus激酶和转录活化因子(JA...旨在探究奶牛乳腺上皮细胞(BMECs)与脐带间充质干细胞(UC-MSCs)共培养对(BMECs)乳脂合成及关键基因表达的影响。试验共分为8组:共培养组为UC-MSCs和BMECs共培养条件下的不处理组、IGF-1R抑制剂AG1024处理组、Janus激酶和转录活化因子(JAK/STAT)信号通路信号阻断剂AG490处理组及AG1024+AG490处理组,对照组为BMECs单培养条件下的不处理组、IGF-1R抑制剂AG1024组、Janus激酶和转录活化因子(JAK/STAT)信号通路信号阻断剂AG490组及AG1024+AG490处理组。检测各组上清IGF-1、甘油三酯(TG)含量变化;RT-qPCR检测乙酰辅酶A羧化酶(ACACA),脂肪酸合成酶(FASN)和固醇调节元件结合蛋白(Sterol regulatory element binding proteins,SREBP1)基因的相对表达丰度。结果表明,共培养组IGF-1、TG含量均显著高于对照组(P<0.05);AG1024处理对IGF-1具有极显著抑制效果(P<0.01),显著降低TG含量及ACACA、FASN、SREBP1mRNA相对表达丰度(P<0.05);AG490处理对ACACA、FASN、SREBP1mRNA的表达无显著影响(P>0.05);AG1024和AG490共同处理较AG1024单独处理各项指标表现差异不显著(P>0.05)。综上表明,脐带间充质干细胞能够通过IGF-1促进乳腺上皮细胞乳脂合成及关键基因的表达,JAK2/STAT5信号通路不参与脐带间充质干细胞对乳腺上皮细胞乳脂调控。展开更多
文摘The existence of mammary epithelial stem cell(MaSC)populations capable of mediating mammary gland development and homeostasis has been established for over a decade.A combination of lineage tracing and mammary gland transplantation studies has affirmed that MaSCs and their downstream progenitors are organized in a hierarchal manner;however,these techniques have failed to illuminate the complete spectrum of epithelial intermediate populations or their spatial and temporal relationships.The advent of single cell sequencing technology has allowed for characterization of highly heterogeneous tissues at high resolution.In the last two years,the remarkable advances in single cell RNA sequencing technologies have been leveraged to address the heterogeneity of the mammary epithelium.These studies have afforded fresh insights into the transcriptional differentiation hierarchy and its chronology.Importantly,these data have led to a major conceptual shift in which the rigid boundaries separating stem,progenitor,and differentiated epithelial populations have been deconstructed,resulting in a new more fluid and flexible model of epithelial differentiation.The emerging view of the mammary epithelial hierarchy has important implications for mammary development,carcinogenesis,and metastasis,providing novel insights into the underlying cellular states that may promote malignant phenotypes.
文摘旨在探究奶牛乳腺上皮细胞(BMECs)与脐带间充质干细胞(UC-MSCs)共培养对(BMECs)乳脂合成及关键基因表达的影响。试验共分为8组:共培养组为UC-MSCs和BMECs共培养条件下的不处理组、IGF-1R抑制剂AG1024处理组、Janus激酶和转录活化因子(JAK/STAT)信号通路信号阻断剂AG490处理组及AG1024+AG490处理组,对照组为BMECs单培养条件下的不处理组、IGF-1R抑制剂AG1024组、Janus激酶和转录活化因子(JAK/STAT)信号通路信号阻断剂AG490组及AG1024+AG490处理组。检测各组上清IGF-1、甘油三酯(TG)含量变化;RT-qPCR检测乙酰辅酶A羧化酶(ACACA),脂肪酸合成酶(FASN)和固醇调节元件结合蛋白(Sterol regulatory element binding proteins,SREBP1)基因的相对表达丰度。结果表明,共培养组IGF-1、TG含量均显著高于对照组(P<0.05);AG1024处理对IGF-1具有极显著抑制效果(P<0.01),显著降低TG含量及ACACA、FASN、SREBP1mRNA相对表达丰度(P<0.05);AG490处理对ACACA、FASN、SREBP1mRNA的表达无显著影响(P>0.05);AG1024和AG490共同处理较AG1024单独处理各项指标表现差异不显著(P>0.05)。综上表明,脐带间充质干细胞能够通过IGF-1促进乳腺上皮细胞乳脂合成及关键基因的表达,JAK2/STAT5信号通路不参与脐带间充质干细胞对乳腺上皮细胞乳脂调控。
