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1.
J Cell Sci ; 135(10)2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35502723

RESUMO

The mammary gland epithelial tree contains two distinct cell populations, luminal and basal. The investigation of how this heterogeneity is developed and how it influences tumorigenesis has been hampered by the need to perform studies on these populations using animal models. Comma-1D is an immortalized mouse mammary epithelial cell line that has unique morphogenetic properties. By performing single-cell RNA-seq studies, we found that Comma-1D cultures consist of two main populations with luminal and basal features, and a smaller population with mixed lineage and bipotent characteristics. We demonstrated that multiple transcription factors associated with the differentiation of the mammary epithelium in vivo also modulate this process in Comma-1D cultures. Additionally, we found that only cells with luminal features were able to acquire transformed characteristics after an oncogenic HER2 (also known as ERBB2) mutant was introduced in their genomes. Overall, our studies characterize, at a single-cell level, the heterogeneity of the Comma-1D cell line and illustrate how Comma-1D cells can be used as an experimental model to study both the differentiation and the transformation processes in vitro.


Assuntos
Neoplasias da Mama , Linhagem Celular , Glândulas Mamárias Animais , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Células Epiteliais , Feminino , Glândulas Mamárias Animais/citologia , Camundongos , Análise de Célula Única
2.
EMBO Rep ; 22(12): e53201, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34633138

RESUMO

During the female lifetime, the expansion of the epithelium dictated by the ovarian cycles is supported by a transient increase in the mammary epithelial stem cell population (MaSCs). Notably, activation of Wnt/ß-catenin signaling is an important trigger for MaSC expansion. Here, we report that the miR-424/503 cluster is a modulator of canonical Wnt signaling in the mammary epithelium. We show that mammary tumors of miR-424(322)/503-depleted mice exhibit activated Wnt/ß-catenin signaling. Importantly, we show a strong association between miR-424/503 deletion and breast cancers with high levels of Wnt/ß-catenin signaling. Moreover, miR-424/503 cluster is required for Wnt-mediated MaSC expansion induced by the ovarian cycles. Lastly, we show that miR-424/503 exerts its function by targeting two binding sites at the 3'UTR of the LRP6 co-receptor and reducing its expression. These results unveil an unknown link between the miR-424/503, regulation of Wnt signaling, MaSC fate, and tumorigenesis.


Assuntos
Epitélio , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Glândulas Mamárias Animais/citologia , MicroRNAs , Via de Sinalização Wnt , Animais , Neoplasias da Mama , Carcinogênese , Linhagem Celular Tumoral , Células Epiteliais/citologia , Epitélio/metabolismo , Feminino , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Ciclo Menstrual , Camundongos , MicroRNAs/genética , Células-Tronco/citologia
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